Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have m...Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.展开更多
Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue...Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue due to anemia,lymph node enlargement,hepatosplenomegaly,thrombocytopenia,symptoms related to high viscosity,and peripheral neuropathy,among others.Despite significant advances in WM treatment,this type of indolent lymphoma remains incurable,with a wide array of patient outcomes(Ruan et al.,2020).In recent years,chimeric antigen receptor T(CAR-T)cell therapy targeting cluster of differentiation 19(CD19)has shown unprecedented response rates and durability in the treatment of B-cell malignancies.In this report,we describe a challenging case of WM that involved multiple extramedullary sites,relapsed,and was refractory to chemotherapy,immunotherapy,and targeted therapy.After anti-CD19 CAR-T cell therapy,the tumor burden significantly decreased and the patient’s condition remained stable at the writing of this report.展开更多
Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclona...Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.展开更多
Invasive fungal infection （IFI） is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. We retrospectively reviewed the records of 408 pat...Invasive fungal infection （IFI） is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. We retrospectively reviewed the records of 408 patients un- dergoing alIo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 （22.5%） episodes suffered proven or probable IFI （4 patients were proven, 88 patients were probable）. Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen （HLA） mismatch, long-time neutropenia, and acute graft-versus-host-disease （GVHD） were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus （CMV） disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival （OS） rate for IFI was significantly lower than that of patients without IFI （41.9% vs. 63.6%, P〈0.01）.展开更多
There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-cha...There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-channel chemical sensor to detect such anomalies which can be used in deep-sea at depths of more than 4 000 m. The design allowed five all-solid-state electrodes to be mounted on it and each (apart from one reference electrode) could be changed according to chemicals to be measured. Two experiments were conducted using the chemical sensors. The first was a shallow-sea trial which included sample measurements and in situ monitoring. pH, Eh, CO3^2- and SO4^2- electrodes were utilized to demonstrate that the chemical sensor was accurate and stable outside the laboratory. In the second experiment, the chemical sensor was integrated with pH, Eh, CO3^2- and H2S electrodes, and was used in 29 scans of the seabed along the Southwest Indian Ridge (SWIR) to detect hydrothermal vents, from which 27 sets of valid data were obtained. Hydrothermal vents were identified by analyzing the chemical anomalies, the primary judging criteria were decreasing voltages of Eh and H2S, matched by increasing voltages of pH and CO3^2- . We proposed that simultaneous detection of changes in these parameters will indicate a hydrothermal vent. Amongst the 27 valid sets of data, five potential hydrothermal vents were targeted using the proposed method. We suggest that our sensors could be widely employed by marine scientists.展开更多
CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancer...CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancers,such as acute promyelocytic leukemia and non-Hodgkin's lymphoma.However,no studies have yet investigated whether CUDC-101 is effective against myeloma.Herein,we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma(MM)cell lines and induces cell apoptosis in a time-and dose-dependent manner.Moreover,CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase(PI3K)and HDAC,and regulated the cell cycle G2/M arrest.Moreover,we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug.Bortezomib is one of the important drugs in MM treatment,and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib.The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade.Collectively,our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib,which provides insights into exploring new strategies for MM treatment.展开更多
BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a ...BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.展开更多
The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly divid...The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly dividedinto two types:plane angle and space angle.Studies show that the influence factors include two aspects of physiology and pathology of the angle,in pathological ways,the disease such as myocardial hypertrophy,myocardial ischemia,hypertension,ventricular arrhythmia has larger clinical significance.In recent years,the research on the risk stratification of the QRS-T angle on sudden death has made great progress,but there are still some disputes about whether the space angle can be replaced by the plane angle and the range of normal value and so on.展开更多
This consensus on multiple myeloma-related bone diseases(MBDs)underscores the importance of a multidisciplinary approach that encompasses hematology,radiology,orthopedics,and additional specialties to tackle its intri...This consensus on multiple myeloma-related bone diseases(MBDs)underscores the importance of a multidisciplinary approach that encompasses hematology,radiology,orthopedics,and additional specialties to tackle its intricate challenges.MBD,a prevalent and debilitating complication of multiple myeloma,leads to bone pain,fractures,and skeletal-related events(SREs),which profoundly impact patients’quality of life.The guidelines offer a thorough framework for diagnosis,treatment,and continual assessment,emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography(PET-CT)and magnetic resonance imaging(MRI).Treatment strategies prioritize the careful application of antimyeloma agents,bisphosphonates,and denosumab to minimize bone loss and decrease SRE risk,complemented by surgical and radiotherapy interventions for structural or pain-related issues.Supportive care measures,including pain management,rehabilitation,nutritional support,and dental evaluations,play a crucial role in enhancing patient outcomes and preserving quality of life.This consensus advocates a standardized,evidencebased approach to managing MBD,ensuring comprehensive and coordinated care for patients.展开更多
Psoriasis patients who are obese tend to have serious clinical manifestations and poor responses to various biological agents in most cases. However, the mechanisms by which obesity exacerbates psoriasis remain enigma...Psoriasis patients who are obese tend to have serious clinical manifestations and poor responses to various biological agents in most cases. However, the mechanisms by which obesity exacerbates psoriasis remain enigmatic. In this study, we found that the abundance of systemic and localized cutaneous neutrophil extracellular traps (NETs) associated with the obesity-induced aggravation of psoriasis was positively correlated with disease severity and that the inhibition of NETs alleviated psoriatic dermatitis in obese mice. Mechanistically, we found that changes in fatty acid composition in obese subjects resulted in the deposition of saturated fatty acids (SFAs), which promoted the release of NETs via the TLR4-MD2/ROS signaling pathway. We further revealed that NETs potentiate IL-17 inflammation, especially γδT17-mediated immune responses, in obesity-exacerbated psoriasis patients. Moreover, SFAs induced a decreased response to anti-IL17A treatment in psoriasis-like mice, whereas the inhibition of NETs improved the beneficial effects of anti-IL17A in psoriasis-like mice with lipid metabolism disorders. Our findings collectively suggest that SFA-induced NETs play a critical role in the exacerbation of obesity-related psoriasis and provide potential new strategies for the clinical treatment of refractory psoriasis patients with lipid metabolism disorders.展开更多
Ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)is a pivotal enzyme that mediates the fixation of CO_(2).As the most abundant protein on earth,Rubisco has a significant impact on global carbon,water,and nitrog...Ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)is a pivotal enzyme that mediates the fixation of CO_(2).As the most abundant protein on earth,Rubisco has a significant impact on global carbon,water,and nitrogen cycles.However,the significantly low carboxylation activity and competing oxygenase activity of Rubisco greatly impede high carbon fixation efficiency.This review first summarizes the current efforts in directly or indirectly modifying plant Rubisco,which has been challenging due to its high conservation and limitations in chloroplast transformation techniques.However,recent advancements in understanding Rubisco biogenesis with the assistance of chaperones have enabled successful heterologous expression of all Rubisco forms,including plant Rubisco,in microorganisms.This breakthrough facilitates the acquisition and evaluation of modified proteins,streamlining the measurement of their activity.Moreover,the establishment of a screening system in E.coli opens up possibilities for obtaining high-performance mutant enzymes through directed evolution.Finally,this review emphasizes the utilization of Rubisco in microorganisms,not only expanding their carbon-fixing capabilities but also holding significant potential for enhancing biotransformation processes.展开更多
Antimicrobial resistance(AMR)remains an urgent and formidable challenge to global public health.Developing new medicines or alternative therapies to address AMR is imperative.Herein,we rationally designed and synthesi...Antimicrobial resistance(AMR)remains an urgent and formidable challenge to global public health.Developing new medicines or alternative therapies to address AMR is imperative.Herein,we rationally designed and synthesized a series of Au(I)-based aggregation-induced emission luminogens(AIEgens)to combat drug-resistant bacterial infections.Through systematic screening,we identified an optimal AIEgen,called complex 5,which can rapidly discriminate between gram-positive(G^(+))and gram-negative bacteria(G^(-))bacteria,and exert robust and broad-spectrum antimicrobial potency against diverse drug-resistant bacterial strains,including those intractable to treat in clinic.Furthermore,extensive testing against a variety of clinical drug-resistant isolates,coupled with the successful treatment of methicillin-resistant Staphylococcus aureus-infected skin wounds unequivocally validates the high efficiency and broad-spectrum activity of complex 5.Therefore,complex 5 emerges as a promising candidate for combating drug-resistant bacterial infections in clinic,and this work provides inspiration for developing new solutions to address the escalating global challenge of AMR.展开更多
To the Editor:Photodynamic therapy(PDT)is an alternative treatment option for port-wine stains(PWSs)and offers several advantages over pulsed dye lasers(PDLs).^([1])However,some patients still experience treatment res...To the Editor:Photodynamic therapy(PDT)is an alternative treatment option for port-wine stains(PWSs)and offers several advantages over pulsed dye lasers(PDLs).^([1])However,some patients still experience treatment resistance and significant side effects.^([1])Optical clearing agent(OCA)has been shown to enhance light penetration in mouse models.^([2])Therefore,we aimed to assess whether combined OCA pretreatment can improve clinical PDT therapy outcomes and investigate the effectiveness of different types of OCA,especially hyaluronic acid microneedles(HA-MNs),in enhancing PDT.展开更多
Scedosporium boydii is considered an opportunist fungal pathogen in immunocompromised patients.It also causes serious and fatal central nervous system infections.In this study,a man with brain abscesses infected with ...Scedosporium boydii is considered an opportunist fungal pathogen in immunocompromised patients.It also causes serious and fatal central nervous system infections.In this study,a man with brain abscesses infected with S.boydii was diagnosed using multiple methods,including microscopy,culture combined with Matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MOLDI-TOF MS),internal transcribed spacer sequencing and Metagenomic next-generation sequencing(mNGS).This successful diagnosis highlights the importance of using a variety of techniques to identify and treat infections caused by this dangerous fungus.展开更多
Early progression of disease within 24 months(POD24)of diagnosis is associated with inferior overall survival(OS)in follicular lymphoma,but its prognostic role in Waldenström’s macroglobulinemia(WM)is still uncl...Early progression of disease within 24 months(POD24)of diagnosis is associated with inferior overall survival(OS)in follicular lymphoma,but its prognostic role in Waldenström’s macroglobulinemia(WM)is still unclear.Here,we per-formed a retrospective analysis of 373 patients pooled from the database of the Chinese Registration Network for WM(CRNWM)to determine the outcomes of early progressors.POD24 occurred in 98 evaluable patients(26.3%).The median OS in patients with POD24 was 40 months(95%CI:15.2–64.0),which was significantly shorter than that with-out POD24(156 months,95%CI:123.6–188.4;HR:6.587,95%CI 4.392–9.881,P<0.0001).Moreover,subgroup analysis showed that POD24 still maintained its predictive ability of inferior OS in patients treated with rituximab or borte-zomib-based treatment.Patients with a very high-risk rIPSSWM stage were more likely to have POD24(P=0.020).In conclusion,POD24 was associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.展开更多
Physiotherapies play a crucial role in noninvasive tissue engineering for wound healing.However,challenges such as the implementation of complex interventions and unsatisfactory treatment outcomes impede widespread ap...Physiotherapies play a crucial role in noninvasive tissue engineering for wound healing.However,challenges such as the implementation of complex interventions and unsatisfactory treatment outcomes impede widespread application.Here,we proposed a stretchable and wirelessly-powered optoelectronic synergistic patch with a dual-layer serpentine wireless receiver circuit to drive the optoelectronic modulation component.Optimized structure and impedance matching enable the patch to seamlessly attach to irregular skin surfaces and operate robustly over a 30%tensile strain range.Based on Sprague-Dawley rat wound model.The wound closure rate of the optoelectronic synergistic group significantly outperformed both monointervention and blank control groups.Mechanistically,optoelectronic synergistic intervention enhances the secretion of vascular endothelial marker proteins and growth factors,and stabilizes mitochondrial function during oxidative stress.Overall,the scalable amalgamation of flexible electronics,wireless transmission,and synergistic interventions promise to improve wound care.展开更多
In this articleQianWang,Siyuan Cai,Guang Yao and Liyuan Zhang should have been denoted as equally contributing authors.In the sentence beginning‘In order to clarify the relationship between...’in this article,the se...In this articleQianWang,Siyuan Cai,Guang Yao and Liyuan Zhang should have been denoted as equally contributing authors.In the sentence beginning‘In order to clarify the relationship between...’in this article,the sentence‘The heating performance of the OESP was stable without passing the batch,with average maximum,minimum,and mean temperatures of 33.52,30.27,and 32.37℃,respectively(Supplementary Fig.6a)’should have read‘The heating performance of the OESP was stable with average maximum,minimum,and mean temperatures of 33.52,30.27,and 32.37℃,respectively(Supplementary Fig.6a)’.The original article has been updated.展开更多
Photosynthetic CO2 fixation is the ultimate source of organic carbon on earth and thus is essential for crop production and carbon sequestration, Ribulose-1,5-bis- phosphate carboxylase/oxygenase （Rubisco） catalyzes...Photosynthetic CO2 fixation is the ultimate source of organic carbon on earth and thus is essential for crop production and carbon sequestration, Ribulose-1,5-bis- phosphate carboxylase/oxygenase （Rubisco） catalyzes the first step of photosynthetic CO2 fixation. However, the extreme low carboxylation efficiency of Rubisco makes it the most attractive target for improving pho- tosynthetic efficiency. Extensive studies have focused on re-engineering a more efficient enzyme, but the effort has been impeded by the limited understanding of its structure-function relationships and the lack of an effi- cient selection system towards its activity. To address the unsuccessful molecular engineering of Rubisco, we developed an Escherichia coil-based activity-directed selection system which links the growth of host cell solely to the Rubisco activity therein. A Synechococcus sp. PCC7002 Rubisco mutant with E49V and D82G sub- stitutions in the small subunit was selected from a total of 15,000 mutants by one round of evolution. This mutant showed an 85% increase in specific carboxyla- tion activity and a 45% improvement in catalytic efficiency towards CO2. The small-subunit E49V mutation was speculated to influence holoenzyme catalysis through interaction with the large-subunit Q225. This interaction is conserved among various Rubisco from higher plants and Chlamydomonas reinhardtii. Knowledge of these might provide clues for engineering Rubisco from higher plants, with the potential of increasing the crop yield.展开更多
Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expre...Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clini- cal management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental ap- proaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method- ologies will continue to extend its application in studying cancer metastasis.展开更多
基金supported by grant from the National Natural Science Foundation of China(Grant No.82300231).
文摘Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.
基金supported by the Zhejiang Key Research and Development Project(No.2020C03014).
文摘Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue due to anemia,lymph node enlargement,hepatosplenomegaly,thrombocytopenia,symptoms related to high viscosity,and peripheral neuropathy,among others.Despite significant advances in WM treatment,this type of indolent lymphoma remains incurable,with a wide array of patient outcomes(Ruan et al.,2020).In recent years,chimeric antigen receptor T(CAR-T)cell therapy targeting cluster of differentiation 19(CD19)has shown unprecedented response rates and durability in the treatment of B-cell malignancies.In this report,we describe a challenging case of WM that involved multiple extramedullary sites,relapsed,and was refractory to chemotherapy,immunotherapy,and targeted therapy.After anti-CD19 CAR-T cell therapy,the tumor burden significantly decreased and the patient’s condition remained stable at the writing of this report.
基金the National Natural Science Foundation of China(Nos.81800201 and 81872322)the Zhejiang Key Research and Development Project(No.2020C03014)the Key Project of Zhejiang Provincial Natural Science Foundation of China(No.LZ22H160009)。
文摘Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.
基金supported by the National Natural Science Foundation of China(Nos.81170526 and 81270640)
文摘Invasive fungal infection （IFI） is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. We retrospectively reviewed the records of 408 patients un- dergoing alIo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 （22.5%） episodes suffered proven or probable IFI （4 patients were proven, 88 patients were probable）. Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen （HLA） mismatch, long-time neutropenia, and acute graft-versus-host-disease （GVHD） were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus （CMV） disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival （OS） rate for IFI was significantly lower than that of patients without IFI （41.9% vs. 63.6%, P〈0.01）.
基金The Open Foundation of Laboratory of Marine Ecosystem and Biogeochemistry,SOA under contract No.LMEB201701
文摘There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-channel chemical sensor to detect such anomalies which can be used in deep-sea at depths of more than 4 000 m. The design allowed five all-solid-state electrodes to be mounted on it and each (apart from one reference electrode) could be changed according to chemicals to be measured. Two experiments were conducted using the chemical sensors. The first was a shallow-sea trial which included sample measurements and in situ monitoring. pH, Eh, CO3^2- and SO4^2- electrodes were utilized to demonstrate that the chemical sensor was accurate and stable outside the laboratory. In the second experiment, the chemical sensor was integrated with pH, Eh, CO3^2- and H2S electrodes, and was used in 29 scans of the seabed along the Southwest Indian Ridge (SWIR) to detect hydrothermal vents, from which 27 sets of valid data were obtained. Hydrothermal vents were identified by analyzing the chemical anomalies, the primary judging criteria were decreasing voltages of Eh and H2S, matched by increasing voltages of pH and CO3^2- . We proposed that simultaneous detection of changes in these parameters will indicate a hydrothermal vent. Amongst the 27 valid sets of data, five potential hydrothermal vents were targeted using the proposed method. We suggest that our sensors could be widely employed by marine scientists.
基金supported by the National Natural Science Foundation of China(Nos.81872322,81900209,and 82100213)the Zhejiang Key Research and Development Project(No.2020C03014)。
文摘CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancers,such as acute promyelocytic leukemia and non-Hodgkin's lymphoma.However,no studies have yet investigated whether CUDC-101 is effective against myeloma.Herein,we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma(MM)cell lines and induces cell apoptosis in a time-and dose-dependent manner.Moreover,CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase(PI3K)and HDAC,and regulated the cell cycle G2/M arrest.Moreover,we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug.Bortezomib is one of the important drugs in MM treatment,and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib.The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade.Collectively,our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib,which provides insights into exploring new strategies for MM treatment.
文摘BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.
文摘The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly dividedinto two types:plane angle and space angle.Studies show that the influence factors include two aspects of physiology and pathology of the angle,in pathological ways,the disease such as myocardial hypertrophy,myocardial ischemia,hypertension,ventricular arrhythmia has larger clinical significance.In recent years,the research on the risk stratification of the QRS-T angle on sudden death has made great progress,but there are still some disputes about whether the space angle can be replaced by the plane angle and the range of normal value and so on.
文摘This consensus on multiple myeloma-related bone diseases(MBDs)underscores the importance of a multidisciplinary approach that encompasses hematology,radiology,orthopedics,and additional specialties to tackle its intricate challenges.MBD,a prevalent and debilitating complication of multiple myeloma,leads to bone pain,fractures,and skeletal-related events(SREs),which profoundly impact patients’quality of life.The guidelines offer a thorough framework for diagnosis,treatment,and continual assessment,emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography(PET-CT)and magnetic resonance imaging(MRI).Treatment strategies prioritize the careful application of antimyeloma agents,bisphosphonates,and denosumab to minimize bone loss and decrease SRE risk,complemented by surgical and radiotherapy interventions for structural or pain-related issues.Supportive care measures,including pain management,rehabilitation,nutritional support,and dental evaluations,play a crucial role in enhancing patient outcomes and preserving quality of life.This consensus advocates a standardized,evidencebased approach to managing MBD,ensuring comprehensive and coordinated care for patients.
基金supported by the National Natural Science Foundation of China(82130089,82103730,82304022,and 32070894)the Key R&D Program of Hubei Province(YFXM2021000203)+1 种基金the National Key Research and Development Program of China(2020YFA0804400)the Program of HUST Academic Frontier Youth Team(2018QYTD10).
文摘Psoriasis patients who are obese tend to have serious clinical manifestations and poor responses to various biological agents in most cases. However, the mechanisms by which obesity exacerbates psoriasis remain enigmatic. In this study, we found that the abundance of systemic and localized cutaneous neutrophil extracellular traps (NETs) associated with the obesity-induced aggravation of psoriasis was positively correlated with disease severity and that the inhibition of NETs alleviated psoriatic dermatitis in obese mice. Mechanistically, we found that changes in fatty acid composition in obese subjects resulted in the deposition of saturated fatty acids (SFAs), which promoted the release of NETs via the TLR4-MD2/ROS signaling pathway. We further revealed that NETs potentiate IL-17 inflammation, especially γδT17-mediated immune responses, in obesity-exacerbated psoriasis patients. Moreover, SFAs induced a decreased response to anti-IL17A treatment in psoriasis-like mice, whereas the inhibition of NETs improved the beneficial effects of anti-IL17A in psoriasis-like mice with lipid metabolism disorders. Our findings collectively suggest that SFA-induced NETs play a critical role in the exacerbation of obesity-related psoriasis and provide potential new strategies for the clinical treatment of refractory psoriasis patients with lipid metabolism disorders.
基金supported by the National Key R&D Program of China(2021YFC2103500)the National Natural Science Foundation of China(32270057)the DNL Cooperation Fund,CAS(DNL202014).
文摘Ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)is a pivotal enzyme that mediates the fixation of CO_(2).As the most abundant protein on earth,Rubisco has a significant impact on global carbon,water,and nitrogen cycles.However,the significantly low carboxylation activity and competing oxygenase activity of Rubisco greatly impede high carbon fixation efficiency.This review first summarizes the current efforts in directly or indirectly modifying plant Rubisco,which has been challenging due to its high conservation and limitations in chloroplast transformation techniques.However,recent advancements in understanding Rubisco biogenesis with the assistance of chaperones have enabled successful heterologous expression of all Rubisco forms,including plant Rubisco,in microorganisms.This breakthrough facilitates the acquisition and evaluation of modified proteins,streamlining the measurement of their activity.Moreover,the establishment of a screening system in E.coli opens up possibilities for obtaining high-performance mutant enzymes through directed evolution.Finally,this review emphasizes the utilization of Rubisco in microorganisms,not only expanding their carbon-fixing capabilities but also holding significant potential for enhancing biotransformation processes.
基金Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Numbers:2021A1515110373,2023A1515011924Science and Technology Planning Project of Guangzhou-Basic and Applied Basic Research Project,Grant/Award Number:202201011505+4 种基金Major Scientific and Technological Special Project in the Precision Medical Field of Guangdong Province,Grant/Award Number:2019B020232003National Key Research and Development Program of China,Grant/Award Numbers:2021YFA1300604,2021YFE0202400National Natural Science Foundation of China,Grant/Award Numbers:22205096,31971293Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University,Grant/Award Number:2021J002National Science Fund for Distinguished Young Scholars,Grant/Award Number:82025024。
文摘Antimicrobial resistance(AMR)remains an urgent and formidable challenge to global public health.Developing new medicines or alternative therapies to address AMR is imperative.Herein,we rationally designed and synthesized a series of Au(I)-based aggregation-induced emission luminogens(AIEgens)to combat drug-resistant bacterial infections.Through systematic screening,we identified an optimal AIEgen,called complex 5,which can rapidly discriminate between gram-positive(G^(+))and gram-negative bacteria(G^(-))bacteria,and exert robust and broad-spectrum antimicrobial potency against diverse drug-resistant bacterial strains,including those intractable to treat in clinic.Furthermore,extensive testing against a variety of clinical drug-resistant isolates,coupled with the successful treatment of methicillin-resistant Staphylococcus aureus-infected skin wounds unequivocally validates the high efficiency and broad-spectrum activity of complex 5.Therefore,complex 5 emerges as a promising candidate for combating drug-resistant bacterial infections in clinic,and this work provides inspiration for developing new solutions to address the escalating global challenge of AMR.
基金supported by grants from the National Natural Science Foundation of China(Nos.82203924,82130089,and 82003366)Key Research Program of Hubei province(No.2021BCA120)China Postdoctoral Science Foundation(No.2022M721265).
文摘To the Editor:Photodynamic therapy(PDT)is an alternative treatment option for port-wine stains(PWSs)and offers several advantages over pulsed dye lasers(PDLs).^([1])However,some patients still experience treatment resistance and significant side effects.^([1])Optical clearing agent(OCA)has been shown to enhance light penetration in mouse models.^([2])Therefore,we aimed to assess whether combined OCA pretreatment can improve clinical PDT therapy outcomes and investigate the effectiveness of different types of OCA,especially hyaluronic acid microneedles(HA-MNs),in enhancing PDT.
文摘Scedosporium boydii is considered an opportunist fungal pathogen in immunocompromised patients.It also causes serious and fatal central nervous system infections.In this study,a man with brain abscesses infected with S.boydii was diagnosed using multiple methods,including microscopy,culture combined with Matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MOLDI-TOF MS),internal transcribed spacer sequencing and Metagenomic next-generation sequencing(mNGS).This successful diagnosis highlights the importance of using a variety of techniques to identify and treat infections caused by this dangerous fungus.
基金supported by grants from the National Nature Science Foundation of China(82370197,81900203,81970187,82170193 and 81920108006)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2022-I2M-1-022 and 2021-I2M-C&T-B-081).
文摘Early progression of disease within 24 months(POD24)of diagnosis is associated with inferior overall survival(OS)in follicular lymphoma,but its prognostic role in Waldenström’s macroglobulinemia(WM)is still unclear.Here,we per-formed a retrospective analysis of 373 patients pooled from the database of the Chinese Registration Network for WM(CRNWM)to determine the outcomes of early progressors.POD24 occurred in 98 evaluable patients(26.3%).The median OS in patients with POD24 was 40 months(95%CI:15.2–64.0),which was significantly shorter than that with-out POD24(156 months,95%CI:123.6–188.4;HR:6.587,95%CI 4.392–9.881,P<0.0001).Moreover,subgroup analysis showed that POD24 still maintained its predictive ability of inferior OS in patients treated with rituximab or borte-zomib-based treatment.Patients with a very high-risk rIPSSWM stage were more likely to have POD24(P=0.020).In conclusion,POD24 was associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.
基金supported by the National Natural Science Foundation of China under grant Nos.61825102(Y.L.),U21A20460(Y.L.),62371115(G.Y.),52021001(Y.L.)Science and Technology Major Project of Tibetan Autonomous Region of China under grant No.XZ202201ZD0001G(G.Y.)+1 种基金Science and Technology Department of Sichuan Province under grant No.24NSFSC1553(G.Y.)the Medico-Engineering Cooperation Funds,Fundamental Research Funds for the Central Universities,UESTC under grant Nos.ZYGX2020ZB041(G.Y.)and ZYGX2021YGLH002(Y.L.).
文摘Physiotherapies play a crucial role in noninvasive tissue engineering for wound healing.However,challenges such as the implementation of complex interventions and unsatisfactory treatment outcomes impede widespread application.Here,we proposed a stretchable and wirelessly-powered optoelectronic synergistic patch with a dual-layer serpentine wireless receiver circuit to drive the optoelectronic modulation component.Optimized structure and impedance matching enable the patch to seamlessly attach to irregular skin surfaces and operate robustly over a 30%tensile strain range.Based on Sprague-Dawley rat wound model.The wound closure rate of the optoelectronic synergistic group significantly outperformed both monointervention and blank control groups.Mechanistically,optoelectronic synergistic intervention enhances the secretion of vascular endothelial marker proteins and growth factors,and stabilizes mitochondrial function during oxidative stress.Overall,the scalable amalgamation of flexible electronics,wireless transmission,and synergistic interventions promise to improve wound care.
文摘In this articleQianWang,Siyuan Cai,Guang Yao and Liyuan Zhang should have been denoted as equally contributing authors.In the sentence beginning‘In order to clarify the relationship between...’in this article,the sentence‘The heating performance of the OESP was stable without passing the batch,with average maximum,minimum,and mean temperatures of 33.52,30.27,and 32.37℃,respectively(Supplementary Fig.6a)’should have read‘The heating performance of the OESP was stable with average maximum,minimum,and mean temperatures of 33.52,30.27,and 32.37℃,respectively(Supplementary Fig.6a)’.The original article has been updated.
文摘Photosynthetic CO2 fixation is the ultimate source of organic carbon on earth and thus is essential for crop production and carbon sequestration, Ribulose-1,5-bis- phosphate carboxylase/oxygenase （Rubisco） catalyzes the first step of photosynthetic CO2 fixation. However, the extreme low carboxylation efficiency of Rubisco makes it the most attractive target for improving pho- tosynthetic efficiency. Extensive studies have focused on re-engineering a more efficient enzyme, but the effort has been impeded by the limited understanding of its structure-function relationships and the lack of an effi- cient selection system towards its activity. To address the unsuccessful molecular engineering of Rubisco, we developed an Escherichia coil-based activity-directed selection system which links the growth of host cell solely to the Rubisco activity therein. A Synechococcus sp. PCC7002 Rubisco mutant with E49V and D82G sub- stitutions in the small subunit was selected from a total of 15,000 mutants by one round of evolution. This mutant showed an 85% increase in specific carboxyla- tion activity and a 45% improvement in catalytic efficiency towards CO2. The small-subunit E49V mutation was speculated to influence holoenzyme catalysis through interaction with the large-subunit Q225. This interaction is conserved among various Rubisco from higher plants and Chlamydomonas reinhardtii. Knowledge of these might provide clues for engineering Rubisco from higher plants, with the potential of increasing the crop yield.
基金supported by Hong Kong Research Grants Council Grants HKU 7227/02M(to Q.Y.H.),HKU 7218/02M and HKU 7395/03M(toJ.F.C.)the Department of Chemistry,and the Areasof Excellence scheme of Hong Kong University GrantsCommittee
文摘Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clini- cal management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental ap- proaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method- ologies will continue to extend its application in studying cancer metastasis.
