BACKGROUND Autoimmune gastritis(AIG)is frequently associated with one or more comorbid conditions,among which type I gastric neuroendocrine tumors(gNETs)warrant significant clinical concern.However,risk factors for th...BACKGROUND Autoimmune gastritis(AIG)is frequently associated with one or more comorbid conditions,among which type I gastric neuroendocrine tumors(gNETs)warrant significant clinical concern.However,risk factors for the development of gNETs in AIG populations remain poorly defined.AIM To characterize the clinical and endoscopic profiles of AIG and identify potential risk factors for gNETs development.METHODS In this single-center cross-sectional study carried out at a tertiary hospital,303 patients with AIG over an 8-year period were retrospectively categorized into gNETs(n=116)and non-gNETs(n=187)groups.Endoscopic and clinical pa-rameters were analyzed.Endoscopic features were systematically reevaluated according to the 2023 Japanese diagnostic criteria for AIG.Feature selection was performed using the Boruta algorithm,and the model discriminative ability was evaluated via receiver operating characteristic curve analysis.RESULTS Among the 303 patients with AIG,116 had gNETs and 187 did not.Compared with the non-gNETs group,patients in the gNETs group were younger(54.3 years vs 60.6 years,P<0.001),had higher rate of vitamin B12 deficiency(77.2%vs 55.8%,P<0.001),lower pepsinogen I(4.3 ng/mL vs 7.4 ng/mL,P<0.001)and pepsinogen I/II ratios(0.7 vs.1.1,P<0.001),and lower prior Helicobacter pylori infection rate(3.4%vs 21.4%,P<0.001).Endoscopically,the gNETs group showed a lower incidence of oxyntic mucosal remnants,hyperplastic polyps,and patchy antral redness.The predictive model incorporating age,prior Helicobacter pylori infection,vitamin B12 level,gastric hy-perplastic polyps,and patchy antral redness showed an area under the curve of 0.830.CONCLUSION Patients with AIG or gNETs exhibit specific clinical and endoscopic features.The predictive model demonstrated favorable discriminative ability and may facilitate risk stratification of gNETs in patients with AIG.展开更多
In saline water flotation, the salinity can cause a distinguishable slime coating of clay minerals on chalcopyrite particles through its effect on their electrical double layers in aqueous solutions. In this work, kao...In saline water flotation, the salinity can cause a distinguishable slime coating of clay minerals on chalcopyrite particles through its effect on their electrical double layers in aqueous solutions. In this work, kaolinite was used as a representative clay mineral for studying slime coating during chalcopyrite flotation. The flotation of chalcopyrite in the presence and absence of kaolinite in tap water, seawater, and gypsum-saturated water and the stability of chalcopyrite and kaolinite particles in slurries are presented. Zeta-potential distributions and scanning electron microscopy images were used to characterize and explain the different slime coating degrees and the different flotation performances. Kaolinite particles induced slime coating on chalcopyrite surfaces and reduced chalcopyrite floatability to the greatest extent when the p H value was in the alkaline range. At 0.24 wt% of kaolinite, the chalcopyrite floatability was depressed by more than 10% at alkaline p H levels in tap water. Salinity in seawater and gypsum-saturated water compressed the electrical double layers and resulted in extensive slime coating.展开更多
Cacao (Theobroma cacao L.) is of significant economic importance in several tropical countries but its yield potentials are low mainly because of poor soil fertility especially low levels of potassium (K). Cacao has a...Cacao (Theobroma cacao L.) is of significant economic importance in several tropical countries but its yield potentials are low mainly because of poor soil fertility especially low levels of potassium (K). Cacao has a high demand for K to maintain healthy growth and production. Knowledge of K use in cacao will help the development of suitable crop management practices and will aid breeding varieties adapted to environments with a limited soil K supply. Using a plant growth chamber, we investigated the growth and physiological traits among three cacao varieties at three levels of growth medium K (52, 156, and 469 mg·plant-1). Significant K effects were observed on growth traits including stem diameter, root length, chlorophyll b, and the ratio of chlorophyll a/b. Significant K effect was also found on carbohydrate metabolites, such as fructose, glucose, myo-inositol, raffinose and starch. However, no K effect was observed in other growth and physiological indicators, including biomass of seedling and net photosynthetic rate. There were significant genotype differences on seedling growth indicators, including stem diameter, stem height, total biomass, leaf biomass, leaf area, root length, chlorophyll a + b and carotenoids. Genotype difference was also found on all measured carbohydrate and starch metabolites, except maltose and raffinose. Results of this study indicate that although K plays a critical role in cacao tree growth and productivity, cacao may be less sensitive to K deficiency during the seedling stage. The present results improved our understanding about K and plants interaction in cacao seedlings, which is useful for crop management and germplasm utilization.展开更多
BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE...BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.展开更多
Objective The aim of the study was to evaluate the characteristics of HIV drug-genotypic resistance among patients taking first-line ARV regimens using polymerase chain reaction and sequencing,and guide to design opti...Objective The aim of the study was to evaluate the characteristics of HIV drug-genotypic resistance among patients taking first-line ARV regimens using polymerase chain reaction and sequencing,and guide to design optimal ARV regimens for these patients.Methods HIV reverse transcriptase-encoded gene was amplified with RT-PCR and amplified PCR products were aligned and comparatively analyzed with HIV resistance database to find drug-resistance mutations.Results Twenty-eight PCR products were amplified and sequenced successfully in 30 serum samples of recruited HIV-infected patients with virologic failure.The resistance rate was 96%,mutations in NRT region were found in 26 patients(93%),while mutations in NNRT region were found in 27 patients(96%).M184V was the most common mutation(86%),K65R was selected in 14%of recruited individuals and TAMs occurred in 50%of patients,which resulted in resistance to NRTIs.Y181C and V179D were the most common mutations in NNRTIs and prevalence was 43%(12/28)and 36%(10/28),respectively,which resulted in cross-resistance to NNRTIs due to low-genetic barrier.Conclusions Virologic failure may occur in long-term administration of first-line ARV regimens,and drugresistance mutations can be found in these patients,which resulted in resistance to first-line ARV regimens.We emphasized that HIV viral load assay and resistance assay were important tools to guide healthcare workers to design an optimal second-line ARV regimens for HAART-experienced individuals with virologic failure.展开更多
The precipitation behavior of nanometer-sized carbides in ferrite in Nb-V-bearing low-carbon steel was studied by electron microscopy and nanoindentation hardness measurements. The results indicated that interphase pr...The precipitation behavior of nanometer-sized carbides in ferrite in Nb-V-bearing low-carbon steel was studied by electron microscopy and nanoindentation hardness measurements. The results indicated that interphase precipitation and random precipitation could occur simultaneously for the specimen isothermally treated at 700 ℃ for 60 min, while in other specimens, only random precipitation was observed. This phenomenon might be explained by mass balance criterion during the diffusional phase transformation. Nanohardness result indicated that the average hardness of the specimens isothermally held at 600 ℃ for 20 min was 3.87 GPa. For the specimen isothermally holding at 650 ℃ for 20 min, the average hardness was 4.10 GPa and the distribution of the nanohardness was in a narrower range compared with that of the specimen isothermal holding at 600 ℃ for 20 min. These implied that the carbides in the specimens isothermal treated at 650℃ were more uniformly dispersed, and the number density of the carbides was greater than that treated at 600 ℃. Using Ashby-Orowan model, the contribution of precipitation strengthening to yield strength was estimated to be 110 MPa for the specimen isothermally treated at the temperature of 650 ℃ for 20 min.展开更多
Dothideomycetes comprise a highly diverse range of fungi characterized mainly by asci with two wall layers(bitunicate asci)and often with fissitunicate dehiscence.Many species are saprobes,with many asexual states com...Dothideomycetes comprise a highly diverse range of fungi characterized mainly by asci with two wall layers(bitunicate asci)and often with fissitunicate dehiscence.Many species are saprobes,with many asexual states comprising important plant pathogens.They are also endophytes,epiphytes,fungicolous,lichenized,or lichenicolous fungi.They occur in terrestrial,freshwater and marine habitats in almost every part of the world.We accept 105 families in Dothideomycetes with the new families Anteagloniaceae,Bambusicolaceae,Biatriosporaceae,Lichenoconiaceae,Muyocopronaceae,Paranectriellaceae,Roussoellaceae,Salsugineaceae,Seynesiopeltidaceae and Thyridariaceae introduced in this paper.Each family is provided with a description and notes,including asexual and asexual states,and if more than one genus is included,the type genus is also characterized.Each family is provided with at least one figure-plate,usually illustrating the type genus,a list of accepted genera,including asexual genera,and a key to these genera.A phylogenetic tree based on four gene combined analysis add support for 64 of the families and 22 orders,including the novel orders,Dyfrolomycetales,Lichenoconiales,Lichenotheliales,Monoblastiales,Natipusillales,Phaeotrichales and Strigulales.The paper is expected to provide a working document on Dothideomycetes which can be modified as new data comes to light.It is hoped that by illustrating types we provide stimulation and interest so that more work is carried out in this remarkable group of fungi.展开更多
Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides...Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.展开更多
Pristine LiNi0.5Mnl.5O4 and FePO4-coated one with Fd-3m space groups were prepared by a sol-gel method. The structure and performance were studied by X-ray diffraction （XRD） rietveld refinement, scanning electron mi...Pristine LiNi0.5Mnl.5O4 and FePO4-coated one with Fd-3m space groups were prepared by a sol-gel method. The structure and performance were studied by X-ray diffraction （XRD） rietveld refinement, scanning electron microscopy （SEM）, high resolution transmission electron microscopy （HRTEM）, energy dispersive spectrometer （EDS） mapping, electrochemical impedance spectroscopy （EIS） and charge- discharge tests, respectively. The lattice parameters of all samples almost remain the same from the Rietveld refinement, revealing that the crystallographic structure has no obvious difference between pris- tine LiNi0.5Mn1.5O4 and FePO4-coated one. All materials show similar morphologies with uniform particle distribution with small particle size, and FePO4 coating does not affect the morphology of LiNi0.5Mnl05O 4 material. EDS mapping and HRTEM show that FePO4 may be successfully wrapped around the surfaces of LiNio.sMnl.s04 particles, and provides an effective coating layer between the electrolyte and the surface of LiNi0.5Mn1.5O4 particles. FePO4 （1 wt%）-coated LiNio.sMnl.504 cathode shows the highest discharge capac- ity at high rate （2 C） among all samples. After 80 cycles, the reversible discharge capacity of FePO4 （1 wt%） coated LiNi0.5Mn0.5O4 is 117 mAh g^-1, but the pristine one only has 50 mAh g^-1. FeP04 coating is an effec- tive and controllable way to stabilize the LiNi0.5Mn1.5O4/electrolyte interface, and avoids the direct con- tact between LiNi0.5Mn1.5O4 powders and electrolyte, then suppresses the side reactions and enhances the electrochemical performance of the LiNi0.5Mn1.5O4.展开更多
Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,th...Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.展开更多
The type specimens of Auerswaldia,Auerswaldiella,Barriopsis,Botryosphaeria,Leptoguignardia,Melanops,Neodeightonia,Phaeobotryon,Phaeobotryosphaeria,Phyllachorella,Pyrenostigme,Saccharata,Sivanesania,Spencermartinsia an...The type specimens of Auerswaldia,Auerswaldiella,Barriopsis,Botryosphaeria,Leptoguignardia,Melanops,Neodeightonia,Phaeobotryon,Phaeobotryosphaeria,Phyllachorella,Pyrenostigme,Saccharata,Sivanesania,Spencermartinsia and Vestergrenia were examined and fresh specimens of Botryosphaeriales were collected from Thailand.This material is used to provide a systematic treatment of Botryosphaeriales based on morphology and phylogeny.Two new genera,Botryobambusa and Cophinforma are introduced and comparedwith existing genera.Four species newto science,Auerswaldia dothiorella,A.lignicola,Botryosphaeria fusispora and Phaeobotryosphaeria eucalypti,are also described and justified.We accept 29 genera in Botryosphaeriales,with Macrovalsaria being newly placed.In the phylogenetic tree,the 114 strains of Botyrosphaeriales included in the analysis cluster into two major clades with 80%,96%and 1.00(MP,ML and BY)support,with Clade A containing the family type of Botryosphaeriaceae,and Clade B containing Phyllosticta,Saccharata and Melanops species.This group may represent Phyllostictaceae.In Clade A the taxa analyzed cluster in eight sub-clades(Clades A1-8).Clade A1 comprises three distinct subclusters corresponding to the genera Diplodia(Diplodia Clade),Neodeightonia(Neodeightonia Clade)and Lasiodiplodia(Lasiodiplodia Clade).Clade A2 clusters into three groups representing Phaeobotryosphaeria(100%),Phaeobotryon(100%)and Barriopsis(94%).Clade A3 incorporates 17 strains that cluster into three well-supported genera(Dothiorella(86%),Spencermartinsia(100%)and Auerswaldia(63%);the position of Macrophomina is not stable.Clade A4 is a single lineage(100%)representing the new genus Botryobambusa.Clade A5 is a wellsupported subclade incorporating Neofussicoccum.Clade A6 represents the type species of Botryosphaeria,three other Botryosphaeria species and two other genera,Neoscytalidium and Cophinforma gen.nov.Clade A7 comprises two Pseudofusicoccum species and Clade A8 has two Aplosporella species.These sub-clades may eventually require separate families but this requires analysis of a much larger dataset.Our data advances the understanding of Botryosphaeriales,there is,however,still much research to be carried out with resolution of families and genera,linkage of sexual and asexual morphs and differentiation of cryptic species.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control ...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus.This has led to a great demand for easy preparation and scalable vaccines,especially in low-income countries.Here,we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein.The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs,which might be capable of protecting the host from infection without systemic toxicity.In addition,the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2.Furthermore,inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection.This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.展开更多
Post-translational modification of proteins by N-phosphorylation of the basic amino acid residues plays important roles in biological processes. The high-energy P–N bond might have contributed to the evolution of pre...Post-translational modification of proteins by N-phosphorylation of the basic amino acid residues plays important roles in biological processes. The high-energy P–N bond might have contributed to the evolution of prebiotic chemistry. N-phosphoryl amino acids(PAAs) can serve as interesting small molecular models for the study of P–N bonds in prebiotic chemical evolution. PAAs are capable of simultaneously producing several important biomolecules such as polypeptides and oligonucleotides under mild reaction conditions. In this review, we describe the chemistry of PAAs, discusse their likely prebiotic origins and their reactivity and how they relate to biological P–N bond species. We also depict a possible prebiotic scenario mediated by PAAs in which PAAs may have acted as one of the essential forces driving prebiotic biomolecules to the first protocell.展开更多
Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity ...Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.展开更多
The type specimens or representative specimens of the potentially dothidealean genera Bagnisiella,Botryochora,Coccostromella,Columnosphaeria,Delphinel la,Dictyodothis,Discosphaerina,Dothidea,Dothiora,Endodothiora,Jaff...The type specimens or representative specimens of the potentially dothidealean genera Bagnisiella,Botryochora,Coccostromella,Columnosphaeria,Delphinel la,Dictyodothis,Discosphaerina,Dothidea,Dothiora,Endodothiora,Jaffuela,Mycoporis,Omphalospora,Pachysacca,Plowrightia,Saccothecium,Stylodothis,Sydowia and Yoshinagaia were examined while,fresh specimens of Aureobasidium pullulans,Dothidea insculpta,Plowrightia ribesia and Saccothecium sepincola were made from Italy and Thailand.An introduction and the history of these genera,their family placement,morphology,and molecular phylogeny are provided.Morphology plus GenBank data are used to provide a systematic treatment of Dothideales.Phylogenetic analysis of LSU,SSU and ITS gene regions was carried out and in the resulting phylogenetic tree the taxa cluster in two clades with high bootstrap support.Clade A comprises Dothideaceae,the family type of Dothideales.The family Dothioraceae is not recognized as a distinct family and is synonymized under Dothideaceae.Neocylindroseptoria is introduced to accommodate Cylindroseptoria pistaciae as it forms a well-supported distinct clade in Dothideaceae.Clade B comprises Aureobasidium,Kabatiella,Pseudoseptoria,Saccothecium and Selenophoma species and Columnosphaeria fagi,for which we propose a new family,Aureobasidiaceae.The recently introduced Sydowia eucalypti also clustered within Clade B and therefore based on morphology and molecular phylogeny a new genus Pseudosydowia is introduced for Sydowia eucalypti.Celosporium laricicola is separated in a distinct clade,and therefore it is placed in Dothideales,genera,incertae sedis.The genera Bagnisiella,Botryochora,Coccostromella,Jaffuela,Lucidascocarpa,Mycoporis,Omphalospora,Pachysacca and Yoshinagaia are excluded from Dothideales and their placements are discussed.展开更多
Alzheimer's disease(AD) is one of the most common types of dementia whose hallmarks include neurofibrillary tangles and senile plaques. The latter are mainly composed of amyloid-β proteins(Aβ), and it's sugg...Alzheimer's disease(AD) is one of the most common types of dementia whose hallmarks include neurofibrillary tangles and senile plaques. The latter are mainly composed of amyloid-β proteins(Aβ), and it's suggested that Aβ may be the causative factor in AD pathogenesis. Immunotherapy targeting Aβ for preventing aggregation of Aβ and mildly clearing amyloid plaques has been a hot topic since 1999. Although the first clinical trial of Aβ vaccine, AN-1792, failed in phase II, its results suggested some key points in the design of Aβ vaccines. Avoiding the possible toxic Aβ specific T cell response and inducing a Th2 type cellular immune response may be beneficial for Aβ immunotherapy. Many associations and research groups are working on Aβ vaccine and some progress has been made in recent years. In this review, we have provided a detailed summary of past Aβ vaccines, which have been sorted by the immunogen, and we also discuss some recent progress and future perspectives.展开更多
Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)repres...Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)represented the first example of a unique dilactone structure containing carbonyl bonded single 5-lactone and tricyclic γ-lactone moieties.Their structures were elucidated by NMR analysis,X-ray crystallography,and ECD calculations.Moreover,we revised the structure of hyperibrin B to hy perm on one I(9)via NMR an alysis,a qua ntum computational chemistry method,and hypothetic bios yn thetic con siderations.Three compounds(5,6,and 9)with significant MDR reversal activity(RF ranging from 61 to 223)were superior to the positive control verapamil(MCF-7/ADR,RF:53;HepG2/ADRz RF:124).Mechanism study for compound 5 indicated that this compound could inhibit the function of P-gp tran sport rather tha n its expressi on,and the possible recog nition mechanism betwee n compo und 5 and P-gp was predicted by molecular docking.展开更多
Neurofibrillary tangles composed of tau protein and senile plaque accumulated by amyloid-β(Aβ)are two hallmarks in Alzheimer disease(AD).In the patients with AD,tau is abnormally hyperphosphorylated,mutated or misfo...Neurofibrillary tangles composed of tau protein and senile plaque accumulated by amyloid-β(Aβ)are two hallmarks in Alzheimer disease(AD).In the patients with AD,tau is abnormally hyperphosphorylated,mutated or misfolding,which endows tau with stronger tendency to aggregate.Tau protein has the potency to mediate neuron toxicity of Aβ.The reduction of tau level ameliorates degeneration of neuron axon.Therefore,many researches are exploring new methods to regulate tau level.This review will mainly focus on small molecules that can directly inhibit tau fibrillation or control tau accumulation by regulating tau phosphorylation process.展开更多
Objective:The current study aimed to profile the demographics,hematological index,and extrinsic factors of patients treated for frostbite in a single center in Southwest China.Methods:We collected the clinical data of...Objective:The current study aimed to profile the demographics,hematological index,and extrinsic factors of patients treated for frostbite in a single center in Southwest China.Methods:We collected the clinical data of patients with frostbite admitted to a regional hospital from January 1st,2009 to January 1st,2019.The baseline information was summarized,and the causes and hematological indexes of frostbite were analyzed.Results:The study cohort comprised 27 patients.The median patient age was 22 years(range 14-81 years).All frostbite injuries occurred between September 22nd and April 27th.Half of the patients were Tibetans.Cold injuries in Tibetan patients were associated with pilgrimage(70%,9/13)and grazing(15%,2/13),while the leading causes of frostbite in Han residents of the Southwest China basin were mandatory fieldwork without protection(36%,5/14)and loss of consciousness(36%,5/14).The hematological examination findings did not significantly differ between amputees and those who did not undergo amputation.Several hematological indexes significantly differed between patients with good outcomes versus those with poor outcomes.Conclusion:To avoid severe frostbite damage,routine mandatory activities like pilgrimage should be conducted under proper protection in extreme weather.Hematological indexes such as the red blood cell count,hematocrit,and hemoglobin level should be monitored closely by first-line medical personnel during hospitalization,as these indexes might indicate the outcome of frostbite.Further research is needed to improve the management of patients with frostbite in Southwest China.展开更多
The order Asterinales comprises a single family,Asterinaceae.In this study,types or specimens of 41 genera of Asterinaceae are re-examined and re-described and illustrated by micrographs.Seventeen genera,namely Asteri...The order Asterinales comprises a single family,Asterinaceae.In this study,types or specimens of 41 genera of Asterinaceae are re-examined and re-described and illustrated by micrographs.Seventeen genera,namely Asterina(type genus),Asterinella,Asterotexis,Batistinula,Cirsosia,Echidnodella,Halbania,Lembosia,Meliolaster,Parasterinopsis,Platypeltella,Prillieuxina,Schenckiella(=Allothyrium),Trichasterina,Trichopeltospora,Uleothyrium and Vizellopsis,are maintained within Asterinaceae.Echidnodes,Lembosiella,Lembosina,Morenoina,and Thyriopsi s are transferred to Aulographaceae based on morphological and molecular characteristics.Anariste is transferred to Micropeltidaceae,while Lembosiopsis is transferred to Mycosphaerellaceae.Placoasterella and Placosoma are morphologically close to taxa in Parmulariaceae,where they are transferred.Aulographina is placed in Teratosphaeriaceae,while Asterodothis,Asterinema,Dothidasteromella,Leveillella,Petrakina and Stephanotheca are transferred to Dothideomycetes,genera incertae sedis.Eupelte,Macowaniella,Maheshwaramyces,Parasterinella,and Vishnumyces are treated as doubtful genera,because of lack of morphological and molecular data.Aphanopeltis,Asterolibertia,Neostomella,Placoasterina,and Symphaster are synonyms of Asterina based on morphology,while Trichamelia,Viegasia,and Yamamotoa are synonyms of Lembosia.The characteristics of each family are discussed and a phylogenetic tree is included.展开更多
文摘BACKGROUND Autoimmune gastritis(AIG)is frequently associated with one or more comorbid conditions,among which type I gastric neuroendocrine tumors(gNETs)warrant significant clinical concern.However,risk factors for the development of gNETs in AIG populations remain poorly defined.AIM To characterize the clinical and endoscopic profiles of AIG and identify potential risk factors for gNETs development.METHODS In this single-center cross-sectional study carried out at a tertiary hospital,303 patients with AIG over an 8-year period were retrospectively categorized into gNETs(n=116)and non-gNETs(n=187)groups.Endoscopic and clinical pa-rameters were analyzed.Endoscopic features were systematically reevaluated according to the 2023 Japanese diagnostic criteria for AIG.Feature selection was performed using the Boruta algorithm,and the model discriminative ability was evaluated via receiver operating characteristic curve analysis.RESULTS Among the 303 patients with AIG,116 had gNETs and 187 did not.Compared with the non-gNETs group,patients in the gNETs group were younger(54.3 years vs 60.6 years,P<0.001),had higher rate of vitamin B12 deficiency(77.2%vs 55.8%,P<0.001),lower pepsinogen I(4.3 ng/mL vs 7.4 ng/mL,P<0.001)and pepsinogen I/II ratios(0.7 vs.1.1,P<0.001),and lower prior Helicobacter pylori infection rate(3.4%vs 21.4%,P<0.001).Endoscopically,the gNETs group showed a lower incidence of oxyntic mucosal remnants,hyperplastic polyps,and patchy antral redness.The predictive model incorporating age,prior Helicobacter pylori infection,vitamin B12 level,gastric hy-perplastic polyps,and patchy antral redness showed an area under the curve of 0.830.CONCLUSION Patients with AIG or gNETs exhibit specific clinical and endoscopic features.The predictive model demonstrated favorable discriminative ability and may facilitate risk stratification of gNETs in patients with AIG.
基金financially supported by the Natural Science Foundation of Hubei Province of China (No.2016CFA013)the Wuhan Science and Technology Bureau of China (No.2016070204020156)the Consejo Nacional de Ciencia y Tecnología (CONACYT) of Mexico (No.270186)
文摘In saline water flotation, the salinity can cause a distinguishable slime coating of clay minerals on chalcopyrite particles through its effect on their electrical double layers in aqueous solutions. In this work, kaolinite was used as a representative clay mineral for studying slime coating during chalcopyrite flotation. The flotation of chalcopyrite in the presence and absence of kaolinite in tap water, seawater, and gypsum-saturated water and the stability of chalcopyrite and kaolinite particles in slurries are presented. Zeta-potential distributions and scanning electron microscopy images were used to characterize and explain the different slime coating degrees and the different flotation performances. Kaolinite particles induced slime coating on chalcopyrite surfaces and reduced chalcopyrite floatability to the greatest extent when the p H value was in the alkaline range. At 0.24 wt% of kaolinite, the chalcopyrite floatability was depressed by more than 10% at alkaline p H levels in tap water. Salinity in seawater and gypsum-saturated water compressed the electrical double layers and resulted in extensive slime coating.
文摘Cacao (Theobroma cacao L.) is of significant economic importance in several tropical countries but its yield potentials are low mainly because of poor soil fertility especially low levels of potassium (K). Cacao has a high demand for K to maintain healthy growth and production. Knowledge of K use in cacao will help the development of suitable crop management practices and will aid breeding varieties adapted to environments with a limited soil K supply. Using a plant growth chamber, we investigated the growth and physiological traits among three cacao varieties at three levels of growth medium K (52, 156, and 469 mg·plant-1). Significant K effects were observed on growth traits including stem diameter, root length, chlorophyll b, and the ratio of chlorophyll a/b. Significant K effect was also found on carbohydrate metabolites, such as fructose, glucose, myo-inositol, raffinose and starch. However, no K effect was observed in other growth and physiological indicators, including biomass of seedling and net photosynthetic rate. There were significant genotype differences on seedling growth indicators, including stem diameter, stem height, total biomass, leaf biomass, leaf area, root length, chlorophyll a + b and carotenoids. Genotype difference was also found on all measured carbohydrate and starch metabolites, except maltose and raffinose. Results of this study indicate that although K plays a critical role in cacao tree growth and productivity, cacao may be less sensitive to K deficiency during the seedling stage. The present results improved our understanding about K and plants interaction in cacao seedlings, which is useful for crop management and germplasm utilization.
文摘BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.
基金The Twelve-fifth Key Project: The Study of Construction of Representative areas for Prevention and Therapy of Fatal Infectious Diseases such AIDS & Viral Hepatitis in Chaoyang District Beijing (2012ZX10004-904)Beijing Natural Science Fund: The evaluation of association between polymorphism of leptin or adiponectin and NAFLD complicated with AIDS (7112065)
文摘Objective The aim of the study was to evaluate the characteristics of HIV drug-genotypic resistance among patients taking first-line ARV regimens using polymerase chain reaction and sequencing,and guide to design optimal ARV regimens for these patients.Methods HIV reverse transcriptase-encoded gene was amplified with RT-PCR and amplified PCR products were aligned and comparatively analyzed with HIV resistance database to find drug-resistance mutations.Results Twenty-eight PCR products were amplified and sequenced successfully in 30 serum samples of recruited HIV-infected patients with virologic failure.The resistance rate was 96%,mutations in NRT region were found in 26 patients(93%),while mutations in NNRT region were found in 27 patients(96%).M184V was the most common mutation(86%),K65R was selected in 14%of recruited individuals and TAMs occurred in 50%of patients,which resulted in resistance to NRTIs.Y181C and V179D were the most common mutations in NNRTIs and prevalence was 43%(12/28)and 36%(10/28),respectively,which resulted in cross-resistance to NNRTIs due to low-genetic barrier.Conclusions Virologic failure may occur in long-term administration of first-line ARV regimens,and drugresistance mutations can be found in these patients,which resulted in resistance to first-line ARV regimens.We emphasized that HIV viral load assay and resistance assay were important tools to guide healthcare workers to design an optimal second-line ARV regimens for HAART-experienced individuals with virologic failure.
基金supported financially by National Science Foundation of China(Grant Nos.51234002,51504064,and 51474064)National Key Research and Development Program 2016YFB0300601+1 种基金China Postdoctoral Science Foundation 2016M591443the Fundamental Research Funds for the Central Universities N160704002,N160708001
文摘The precipitation behavior of nanometer-sized carbides in ferrite in Nb-V-bearing low-carbon steel was studied by electron microscopy and nanoindentation hardness measurements. The results indicated that interphase precipitation and random precipitation could occur simultaneously for the specimen isothermally treated at 700 ℃ for 60 min, while in other specimens, only random precipitation was observed. This phenomenon might be explained by mass balance criterion during the diffusional phase transformation. Nanohardness result indicated that the average hardness of the specimens isothermally held at 600 ℃ for 20 min was 3.87 GPa. For the specimen isothermally holding at 650 ℃ for 20 min, the average hardness was 4.10 GPa and the distribution of the nanohardness was in a narrower range compared with that of the specimen isothermal holding at 600 ℃ for 20 min. These implied that the carbides in the specimens isothermal treated at 650℃ were more uniformly dispersed, and the number density of the carbides was greater than that treated at 600 ℃. Using Ashby-Orowan model, the contribution of precipitation strengthening to yield strength was estimated to be 110 MPa for the specimen isothermally treated at the temperature of 650 ℃ for 20 min.
基金We also thank Siriporn Luesuwan for arranging the loan of specimens from various herbaria.A.Ariyawansa and J.C Kang are grateful to the International collaboration plan of Science and Technology at Guizhou Province(contract No.[2012]7006)the construction of innovation talent team of Science and Technology at Guizhou Province(contract No.[2012]4007)+19 种基金China.D.J.Bhat is thankful to MFU for a Visiting Professorship during the tenure of which this paper was finalized.D.L.Hawksworth contributed to this work while in receipt of support from the Spanish Ministerio de Ciencia e Innovación(CGL2011-25003)Haixia Wu would like to thank the Grant for Essential Scientific Research of National Non-profit Institute to funds for research(No.CAFYBB2007002)thanks Xiaoming Chen,Ying Feng and Chen Hang(The Research Institute of Resource Insects,Chinese Academy of Forestry,China)for their valuable help.Jian-Kui Liu would like to thank Manfred Binder for providing valuable suggestions and kind assistance on phylogenetic analysisWe would like to thank MFU grant No.56101020032 for funding to study taxonomy and phylogeny of selected families of DothideomycetesJiye Yan and Xinghong Li would like to thank CARS-30 for funds.K.Tanaka would like to thank the Japan Society for the Promotion of Science(JSPS,25440199)for financial supportK.L.Pang would like to thank National Science Council of Taiwan for financial support(NSC101-2621-B-019-001-MY3).L.Muggia is grateful to the Austrian Science Foundation for financial support(FWF,P24114-B16 and Herta-Firnberg Project T481-B20)M.Doilom would like to thank the Thailand Research Fund through the Royal Golden Jubilee(RGJ)Ph.D.Program grant No.Ph.D./0072/2553 in 4.S.M.F./53/A.2MP Nelsen and R Lücking are grateful to the NSF(DEB 0715660“Neotropical Epiphytic Microlichens-An Innovative Inventory of a Highly Diverse yet Little Known Group of Symbiotic Organisms”DEB 0717476“Systematics of Dothideomycetes”)MP Nelsen also acknowledges a Brown Family Fellowship through the Field Museum,a William Harper Rainey Fellowship through the University of Chicago,and support through the Committee on Evolutionary Biology at the University of Chicago.R.Phookamsak would like to thank the Royal Golden Jubilee Ph.D.Program(PHD/0090/2551)under the Thailand Research Fund for scholarship supportS.A.Alias would like to thank Program Rakan University Malaya(PRPUM)-Phylogeny,Taxonomy,Relationships and Biotechnological Potential of Sooty Moulds.S.Boonmee also thanks Amy Y.Rossman and the U.S.Department of Agriculture Agricultural Research Service,Systematic Mycology and Microbiology Lab(SMML)USA for laboratory,funding support and advice on her work.S.Boonmee and P.Chomnunti would like to thank TRF/BIOTEC program Biodiversity Research and Training Grant BRT R_251181,BRT R_253012the Mushroom Research Foundation,Chiang Rai Province for funding support.S.Wikee would like to thank the Thailand Research Fund through the Royal Golden Jubilee Ph.D.Program agreement No PhD/0198/2552S.Wikee and JK Liu would like to thank The National Research Council of Thailand(NRCT)for the award of grant No 55201020002 to study the genus Phyllosticta in ThailandS.Suetrong acknowledges the financial support by TRF/BIOTEC program Biodiversity Research and Training Grant BRT R_351004 and BRT R_325015 to study marine fungi of ThailandSuetrong also thanks Morakot Tanticharoen,Kanyawim Kirtikara and Lily Eurwilaichitr,BIOTEC,Bangkok for their continued interest and support.Supalak Yacharoen,J.Monkai and K.D.Hyde would like to thank the Thailand Research Fund(BRG5280002)for financial supportGareth Jones is supported by the Distinguished Scientist Fellowship Program(DSFP),King Saud University,Saudi Arabia.Y.Wang would like to thank The International Scientific Cooperated Project of Guizhou Province(No[2013]7004)Yongxiang Liu would like to thank the Guizhou Research Fund(QKHZYZ[2010]5031 and QNKYYZX[2012]010)for financial supportHarrie Sipman is thanked for comments on part of the manuscript.
文摘Dothideomycetes comprise a highly diverse range of fungi characterized mainly by asci with two wall layers(bitunicate asci)and often with fissitunicate dehiscence.Many species are saprobes,with many asexual states comprising important plant pathogens.They are also endophytes,epiphytes,fungicolous,lichenized,or lichenicolous fungi.They occur in terrestrial,freshwater and marine habitats in almost every part of the world.We accept 105 families in Dothideomycetes with the new families Anteagloniaceae,Bambusicolaceae,Biatriosporaceae,Lichenoconiaceae,Muyocopronaceae,Paranectriellaceae,Roussoellaceae,Salsugineaceae,Seynesiopeltidaceae and Thyridariaceae introduced in this paper.Each family is provided with a description and notes,including asexual and asexual states,and if more than one genus is included,the type genus is also characterized.Each family is provided with at least one figure-plate,usually illustrating the type genus,a list of accepted genera,including asexual genera,and a key to these genera.A phylogenetic tree based on four gene combined analysis add support for 64 of the families and 22 orders,including the novel orders,Dyfrolomycetales,Lichenoconiales,Lichenotheliales,Monoblastiales,Natipusillales,Phaeotrichales and Strigulales.The paper is expected to provide a working document on Dothideomycetes which can be modified as new data comes to light.It is hoped that by illustrating types we provide stimulation and interest so that more work is carried out in this remarkable group of fungi.
基金supported by the National Key R&D Program of China(nos.2019YFA0904200 and 2018YFA0507600)the Tsinghua University Spring Breeze Fund(no.2020Z99CFY042)+1 种基金the National Natural Science Foundation of China(nos.92053108 and 31961143004)NCC Fund(no.NCC2020FH04).
文摘Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.
基金supported by the National Natural Science Foundation of China(51404002)Anhui Provincial Natural Science Foundation(1508085MB25)+1 种基金Natural Science Foundation of Guangdong Province(2016A030310127)Anhui Provincial Science Fund for Excellent Young Scholars(gxyqZD2016066)
文摘Pristine LiNi0.5Mnl.5O4 and FePO4-coated one with Fd-3m space groups were prepared by a sol-gel method. The structure and performance were studied by X-ray diffraction （XRD） rietveld refinement, scanning electron microscopy （SEM）, high resolution transmission electron microscopy （HRTEM）, energy dispersive spectrometer （EDS） mapping, electrochemical impedance spectroscopy （EIS） and charge- discharge tests, respectively. The lattice parameters of all samples almost remain the same from the Rietveld refinement, revealing that the crystallographic structure has no obvious difference between pris- tine LiNi0.5Mn1.5O4 and FePO4-coated one. All materials show similar morphologies with uniform particle distribution with small particle size, and FePO4 coating does not affect the morphology of LiNi0.5Mnl05O 4 material. EDS mapping and HRTEM show that FePO4 may be successfully wrapped around the surfaces of LiNio.sMnl.s04 particles, and provides an effective coating layer between the electrolyte and the surface of LiNi0.5Mn1.5O4 particles. FePO4 （1 wt%）-coated LiNio.sMnl.504 cathode shows the highest discharge capac- ity at high rate （2 C） among all samples. After 80 cycles, the reversible discharge capacity of FePO4 （1 wt%） coated LiNi0.5Mn0.5O4 is 117 mAh g^-1, but the pristine one only has 50 mAh g^-1. FeP04 coating is an effec- tive and controllable way to stabilize the LiNi0.5Mn1.5O4/electrolyte interface, and avoids the direct con- tact between LiNi0.5Mn1.5O4 powders and electrolyte, then suppresses the side reactions and enhances the electrochemical performance of the LiNi0.5Mn1.5O4.
基金the National Key R&D Program of China(grant nos.2019YFA0904200 and 2018YFA0507600)the National Natural Science Foundation of China(grant nos.22237003 and 92053108)the Tsinghua University Spring Breeze Fund(grant no.2020Z99CFY042).
文摘Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.
基金We are grateful to the Directors and Curators of the following herbaria for the loan of specimens in their keeping:BAFC,BPI,IMI,K(M),LPS,PREM,S and ZT.The Mushroom Research Foundation,Bandoo District,Chiang Rai Province,Thailand is acknowledged for providing postgraduate scholarship support and facilities to JK Liu.Appreciation is extended to the Thailand Research Fund BRG528002 for supporting this work.
文摘The type specimens of Auerswaldia,Auerswaldiella,Barriopsis,Botryosphaeria,Leptoguignardia,Melanops,Neodeightonia,Phaeobotryon,Phaeobotryosphaeria,Phyllachorella,Pyrenostigme,Saccharata,Sivanesania,Spencermartinsia and Vestergrenia were examined and fresh specimens of Botryosphaeriales were collected from Thailand.This material is used to provide a systematic treatment of Botryosphaeriales based on morphology and phylogeny.Two new genera,Botryobambusa and Cophinforma are introduced and comparedwith existing genera.Four species newto science,Auerswaldia dothiorella,A.lignicola,Botryosphaeria fusispora and Phaeobotryosphaeria eucalypti,are also described and justified.We accept 29 genera in Botryosphaeriales,with Macrovalsaria being newly placed.In the phylogenetic tree,the 114 strains of Botyrosphaeriales included in the analysis cluster into two major clades with 80%,96%and 1.00(MP,ML and BY)support,with Clade A containing the family type of Botryosphaeriaceae,and Clade B containing Phyllosticta,Saccharata and Melanops species.This group may represent Phyllostictaceae.In Clade A the taxa analyzed cluster in eight sub-clades(Clades A1-8).Clade A1 comprises three distinct subclusters corresponding to the genera Diplodia(Diplodia Clade),Neodeightonia(Neodeightonia Clade)and Lasiodiplodia(Lasiodiplodia Clade).Clade A2 clusters into three groups representing Phaeobotryosphaeria(100%),Phaeobotryon(100%)and Barriopsis(94%).Clade A3 incorporates 17 strains that cluster into three well-supported genera(Dothiorella(86%),Spencermartinsia(100%)and Auerswaldia(63%);the position of Macrophomina is not stable.Clade A4 is a single lineage(100%)representing the new genus Botryobambusa.Clade A5 is a wellsupported subclade incorporating Neofussicoccum.Clade A6 represents the type species of Botryosphaeria,three other Botryosphaeria species and two other genera,Neoscytalidium and Cophinforma gen.nov.Clade A7 comprises two Pseudofusicoccum species and Clade A8 has two Aplosporella species.These sub-clades may eventually require separate families but this requires analysis of a much larger dataset.Our data advances the understanding of Botryosphaeriales,there is,however,still much research to be carried out with resolution of families and genera,linkage of sexual and asexual morphs and differentiation of cryptic species.
基金This work was supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2018YFA0507600)Tsinghua University Spring Breeze Fund(No.2020Z99CFY042)+1 种基金the National Natural Science Foundation of China(No.92053108)Applications for Chinese patents related to chitosan-mediated inhalable nanovaccine has been submitted(Patent No.202111130951.7)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus.This has led to a great demand for easy preparation and scalable vaccines,especially in low-income countries.Here,we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein.The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs,which might be capable of protecting the host from infection without systemic toxicity.In addition,the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2.Furthermore,inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection.This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.
基金supported by the National Basic Research Program of China(2013CB910700,2012CB821600)the National Natural Science Foundation of China(21232005,21375113,21305115)the Program of Chinese Ministry of Education for Changjiang Scholars and Innovative Research Team in University
文摘Post-translational modification of proteins by N-phosphorylation of the basic amino acid residues plays important roles in biological processes. The high-energy P–N bond might have contributed to the evolution of prebiotic chemistry. N-phosphoryl amino acids(PAAs) can serve as interesting small molecular models for the study of P–N bonds in prebiotic chemical evolution. PAAs are capable of simultaneously producing several important biomolecules such as polypeptides and oligonucleotides under mild reaction conditions. In this review, we describe the chemistry of PAAs, discusse their likely prebiotic origins and their reactivity and how they relate to biological P–N bond species. We also depict a possible prebiotic scenario mediated by PAAs in which PAAs may have acted as one of the essential forces driving prebiotic biomolecules to the first protocell.
基金supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2018YFA0507600)Tsinghua University Spring Breeze Fund(No.2020Z99CFY042)the National Natural Science Foundation of China(No.92053108).
文摘Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.
文摘The type specimens or representative specimens of the potentially dothidealean genera Bagnisiella,Botryochora,Coccostromella,Columnosphaeria,Delphinel la,Dictyodothis,Discosphaerina,Dothidea,Dothiora,Endodothiora,Jaffuela,Mycoporis,Omphalospora,Pachysacca,Plowrightia,Saccothecium,Stylodothis,Sydowia and Yoshinagaia were examined while,fresh specimens of Aureobasidium pullulans,Dothidea insculpta,Plowrightia ribesia and Saccothecium sepincola were made from Italy and Thailand.An introduction and the history of these genera,their family placement,morphology,and molecular phylogeny are provided.Morphology plus GenBank data are used to provide a systematic treatment of Dothideales.Phylogenetic analysis of LSU,SSU and ITS gene regions was carried out and in the resulting phylogenetic tree the taxa cluster in two clades with high bootstrap support.Clade A comprises Dothideaceae,the family type of Dothideales.The family Dothioraceae is not recognized as a distinct family and is synonymized under Dothideaceae.Neocylindroseptoria is introduced to accommodate Cylindroseptoria pistaciae as it forms a well-supported distinct clade in Dothideaceae.Clade B comprises Aureobasidium,Kabatiella,Pseudoseptoria,Saccothecium and Selenophoma species and Columnosphaeria fagi,for which we propose a new family,Aureobasidiaceae.The recently introduced Sydowia eucalypti also clustered within Clade B and therefore based on morphology and molecular phylogeny a new genus Pseudosydowia is introduced for Sydowia eucalypti.Celosporium laricicola is separated in a distinct clade,and therefore it is placed in Dothideales,genera,incertae sedis.The genera Bagnisiella,Botryochora,Coccostromella,Jaffuela,Lucidascocarpa,Mycoporis,Omphalospora,Pachysacca and Yoshinagaia are excluded from Dothideales and their placements are discussed.
基金supported by the National Basic Research Program of China(2013CB910700,2012CB821600)the National Natural Science Foundation of China(21472109,21102082)the Research Project of Chinese Ministry of Education(113005A)
文摘Alzheimer's disease(AD) is one of the most common types of dementia whose hallmarks include neurofibrillary tangles and senile plaques. The latter are mainly composed of amyloid-β proteins(Aβ), and it's suggested that Aβ may be the causative factor in AD pathogenesis. Immunotherapy targeting Aβ for preventing aggregation of Aβ and mildly clearing amyloid plaques has been a hot topic since 1999. Although the first clinical trial of Aβ vaccine, AN-1792, failed in phase II, its results suggested some key points in the design of Aβ vaccines. Avoiding the possible toxic Aβ specific T cell response and inducing a Th2 type cellular immune response may be beneficial for Aβ immunotherapy. Many associations and research groups are working on Aβ vaccine and some progress has been made in recent years. In this review, we have provided a detailed summary of past Aβ vaccines, which have been sorted by the immunogen, and we also discuss some recent progress and future perspectives.
基金supported by the National Natural Science Foundation of China(Nos.U1812403,81872772,and 81960546)the Scie nee and Tech no logy Departme nt of Guizhou Province(Nos.QKH 2020-1Z076,QKHZC[2020]4Y203z QKHJC[2018]1409,QKHZC[2019]2762,and QKHPTRC[2020]5008)+3 种基金the High-level Innovative Talents in Guizhou Provinee(Thousand Levels of Talent for Chunmao Yuan in 2018)the"Light of the West"Talent Cultivation Program of Chinese Academy of Sciences for Chunmao Yuan(No.RZ[2020]82)the 100 Leading Talents of Guizhou Provinee(fund for Y.M.L)the Guizhou Provincial Engineering Research Center for Natural Drugs.
文摘Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)represented the first example of a unique dilactone structure containing carbonyl bonded single 5-lactone and tricyclic γ-lactone moieties.Their structures were elucidated by NMR analysis,X-ray crystallography,and ECD calculations.Moreover,we revised the structure of hyperibrin B to hy perm on one I(9)via NMR an alysis,a qua ntum computational chemistry method,and hypothetic bios yn thetic con siderations.Three compounds(5,6,and 9)with significant MDR reversal activity(RF ranging from 61 to 223)were superior to the positive control verapamil(MCF-7/ADR,RF:53;HepG2/ADRz RF:124).Mechanism study for compound 5 indicated that this compound could inhibit the function of P-gp tran sport rather tha n its expressi on,and the possible recog nition mechanism betwee n compo und 5 and P-gp was predicted by molecular docking.
基金the Major State Basic Research Development Program of China(Nos.2013CB910700,2012CB821600)the National Natural Science Foundation of China(Nos.21261130090,91313301,21102082 and 21472109)the Research Project of Chinese Ministry of Education(No.113005A).
文摘Neurofibrillary tangles composed of tau protein and senile plaque accumulated by amyloid-β(Aβ)are two hallmarks in Alzheimer disease(AD).In the patients with AD,tau is abnormally hyperphosphorylated,mutated or misfolding,which endows tau with stronger tendency to aggregate.Tau protein has the potency to mediate neuron toxicity of Aβ.The reduction of tau level ameliorates degeneration of neuron axon.Therefore,many researches are exploring new methods to regulate tau level.This review will mainly focus on small molecules that can directly inhibit tau fibrillation or control tau accumulation by regulating tau phosphorylation process.
基金The study was supported by the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC21036)National Natural Science Foundation of China(No.82003373).
文摘Objective:The current study aimed to profile the demographics,hematological index,and extrinsic factors of patients treated for frostbite in a single center in Southwest China.Methods:We collected the clinical data of patients with frostbite admitted to a regional hospital from January 1st,2009 to January 1st,2019.The baseline information was summarized,and the causes and hematological indexes of frostbite were analyzed.Results:The study cohort comprised 27 patients.The median patient age was 22 years(range 14-81 years).All frostbite injuries occurred between September 22nd and April 27th.Half of the patients were Tibetans.Cold injuries in Tibetan patients were associated with pilgrimage(70%,9/13)and grazing(15%,2/13),while the leading causes of frostbite in Han residents of the Southwest China basin were mandatory fieldwork without protection(36%,5/14)and loss of consciousness(36%,5/14).The hematological examination findings did not significantly differ between amputees and those who did not undergo amputation.Several hematological indexes significantly differed between patients with good outcomes versus those with poor outcomes.Conclusion:To avoid severe frostbite damage,routine mandatory activities like pilgrimage should be conducted under proper protection in extreme weather.Hematological indexes such as the red blood cell count,hematocrit,and hemoglobin level should be monitored closely by first-line medical personnel during hospitalization,as these indexes might indicate the outcome of frostbite.Further research is needed to improve the management of patients with frostbite in Southwest China.
基金the Chinese Academy of Sciences,project number 2013T2S0030,for the award of Visiting Professorship for Senior International Scientists at Kunming Institute of Botanya research grant from Mae Fah Luang University,grant number 56101020032 to study Dothideomycetes in Thailand+2 种基金the Biodiversity Research and Training Program(BRTR253012)The Thailand Research Fund(BRG5280002)provided by the Grant for Essential Scientific Research of National Non–profit Institute(no.CAFYBB2007002).
文摘The order Asterinales comprises a single family,Asterinaceae.In this study,types or specimens of 41 genera of Asterinaceae are re-examined and re-described and illustrated by micrographs.Seventeen genera,namely Asterina(type genus),Asterinella,Asterotexis,Batistinula,Cirsosia,Echidnodella,Halbania,Lembosia,Meliolaster,Parasterinopsis,Platypeltella,Prillieuxina,Schenckiella(=Allothyrium),Trichasterina,Trichopeltospora,Uleothyrium and Vizellopsis,are maintained within Asterinaceae.Echidnodes,Lembosiella,Lembosina,Morenoina,and Thyriopsi s are transferred to Aulographaceae based on morphological and molecular characteristics.Anariste is transferred to Micropeltidaceae,while Lembosiopsis is transferred to Mycosphaerellaceae.Placoasterella and Placosoma are morphologically close to taxa in Parmulariaceae,where they are transferred.Aulographina is placed in Teratosphaeriaceae,while Asterodothis,Asterinema,Dothidasteromella,Leveillella,Petrakina and Stephanotheca are transferred to Dothideomycetes,genera incertae sedis.Eupelte,Macowaniella,Maheshwaramyces,Parasterinella,and Vishnumyces are treated as doubtful genera,because of lack of morphological and molecular data.Aphanopeltis,Asterolibertia,Neostomella,Placoasterina,and Symphaster are synonyms of Asterina based on morphology,while Trichamelia,Viegasia,and Yamamotoa are synonyms of Lembosia.The characteristics of each family are discussed and a phylogenetic tree is included.
