Triple negative breast cancer(TNBC)is an exceptionally aggressive subtype of breast cancer with a poor prognosis.TNBC patients have limited treatment options beyond conventional chemotherapy,and they face significant ...Triple negative breast cancer(TNBC)is an exceptionally aggressive subtype of breast cancer with a poor prognosis.TNBC patients have limited treatment options beyond conventional chemotherapy,and they face significant challenges associated with disease recurrence and resistance to chemotherapy.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway plays a pivotal role in cell proliferation,growth,metabolism,and survival.Its aberrant activation is closely linked to the development and progression of TNBC,as well as treatment response and drug resistance.Currently,numerous targeted drugs specifically inhibiting this signaling pathway are being developed and undergoing clinical trials.These include inhibitors targeting PI3K,AKT,or mTOR individually,as well as dual-target or multi-target inhibitors simultaneously targeting different components of this pathway.Encouragingly,some inhibitors have demonstrated promising potential in clinical trials.This review delves into the therapeutic potential of the PI3K/AKT/mTOR signaling pathway for TNBC and explores prospects for drug discovery.展开更多
Objective Cigarette smoking exacerbates the progression of pulmonary tuberculosis(TB).The role of tertiary lymphoid structures(TLS)in chronic lung diseases has gained attention;however,it remains unclear whether smoki...Objective Cigarette smoking exacerbates the progression of pulmonary tuberculosis(TB).The role of tertiary lymphoid structures(TLS)in chronic lung diseases has gained attention;however,it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS.This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB.Methods Lung tissues from 36 male patients(18 smokers and 18 non-smokers)who underwent surgical resection for pulmonary TB were included in this study.Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS,and chest computed tomography(CT)was used to assess the severity of lung lesions.The correlation between the TLS quantity and TB lesion severity scores was analyzed.The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers.Results Smoker patients with TB had significantly higher TLS than non-smokers(P<0.001).The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT(parenchyma:r=0.5767;peribronchial:r=0.7373;both P<0.001).Immunohistochemical analysis showed increased B cells,T cells,and C-X-C motif chemokine ligand 13(CXCL13)expression in smoker patients with TB(P<0.001).Conclusion Smoker TB patients exhibited increased pulmonary TLS,which was associated with exacerbated lung lesions on chest CT,suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.展开更多
With the development of the current era,China’s Internet and computer technologies are constantly updated and improved.Under the application of information technology,great changes have taken place in the financial m...With the development of the current era,China’s Internet and computer technologies are constantly updated and improved.Under the application of information technology,great changes have taken place in the financial management work of schools.At present,the content of school financial management work is constantly increasing.In order to meet the needs of school management,it is necessary to improve the level of financial management,strengthen the informatization construction of financial management,so as to realize the modernization of school financial management and improve the efficiency of financial management.Big data technology and information technology can realize the rapid collection and preprocessing of information,achieve in-depth mining of data value,assist staff in quickly identifying problems in their work,and further improve work efficiency.Based on this,this paper conducts in-depth analysis and research on the informatization construction of financial management in colleges and universities on the basis of big data,for reference.展开更多
A recent progress in new emerging two-dimensional(2 D)materials has provided promising opportunity for gas sensing in ultra-low detectable concentration.In this work,we have demonstrated a flexible NO2 gas sensor with...A recent progress in new emerging two-dimensional(2 D)materials has provided promising opportunity for gas sensing in ultra-low detectable concentration.In this work,we have demonstrated a flexible NO2 gas sensor with porous structure graphene on polyethylene terephthalate substrates operating at room temperature.The gas sensor exhibited good performance with response of 1.2%and a fast response time within 30 s after exposure to50×10^-9 NO2 gas.As porous structure of graphene increased the surface area,the sensor showed high sensitivity of ppb level for NO2 detection.Au nanoparticles were decorated on the surface of the porous structure graphene skeleton,resulting in an incensement of response compared with pristine graphene.Au nanoparticles-decorated graphene exhibits not only better sensitivity(1.5-1.6 times larger than pristine graphene)for NO2 gas detection,but also fast response.The sensor was found to be robust and sensitive under the cycling bending test,which could also be ascribed to the merits of graphene.This porous structure graphene-based gas sensor is expected to enable a simple and inexpensive flexible gas sensing platform.展开更多
This paper is concerned with the dynamic behaviors of wave propagation in layered periodic composites consisting of piezoelectric and piezomagnetic phases. The dispersion relations of Lamb waves axe derived. Dispersio...This paper is concerned with the dynamic behaviors of wave propagation in layered periodic composites consisting of piezoelectric and piezomagnetic phases. The dispersion relations of Lamb waves axe derived. Dispersion curves and displacement fields are calculated with different piezoelectric volume fractions. Numerical results for BaTiO3/CoFe2O4 composites show that the dispersion curves resemble the symmetric Lamb waves in a plate. Exchange between the longitudinal （i.e. thickness） mode and coupled mode takes place at the crossover point between dispersion curves of the first two branches. With the increase of BaTiO3 volume fraction, the crossover point appears at a lower wave number and wave velocity is higher. These findings are useful for magnetoelectric transducer applications.展开更多
The Multiple-Input Multiple-Output(MIMO)Non-Orthogonal Multiple Access(NOMA)based on Spatial Modulation(SM-MIMO-NOMA)system has been proposed to achieve better spectral efficiency with reduced radio frequency chains c...The Multiple-Input Multiple-Output(MIMO)Non-Orthogonal Multiple Access(NOMA)based on Spatial Modulation(SM-MIMO-NOMA)system has been proposed to achieve better spectral efficiency with reduced radio frequency chains comparing to the traditional MIMO-NOMA system.To improve the performance of SM-MIMO-NOMA systems,we extend them to generalized spatial modulation scenarios while maintaining moderate complexity and fairness.In this paper,system spectral efficiency and transmission quality improvements are proposed by investigating a sum-rate maximization resource allocation problem that is subject to the total transmitted power,user grouping,and resource block constraints.To solve this non-convex and difficult problem,a graph-based user grouping strategy is proposed initially to maximize the mutual gains of intragroup users.An auxiliary-variable approach is then adopted to transform the power allocation subproblem into a convex one.Simulation results demonstrate that the proposed algorithm has better performance in terms of bit error rate and sum rates.展开更多
A high-PSRR high-order curvature-compensated CMOS bandgap voltage reference( BGR),which has the performances of high power supply rejection ratio( PSRR) and low temperature coefficient,is designed in SMIC 0. 18 μm CM...A high-PSRR high-order curvature-compensated CMOS bandgap voltage reference( BGR),which has the performances of high power supply rejection ratio( PSRR) and low temperature coefficient,is designed in SMIC 0. 18 μm CMOS process. Compared to the conventional curvature-compensated BGR which adopted a piecewise-linear current,the temperature characterize of the proposed BGR is effectively improved by adopting two kinds of current including a piecewise-linear current and a current proportional 1. 5 party to the absolute temperature T. By adopting a low dropout( LDO) regulator whose output voltage is the operating supply voltage of the proposed BGR core circuit instead of power supply voltage VDD,the proposed BGR with LDO regulator achieves a well PSRR performance than the BGR without LDO regulator. Simulation results show that the proposed BGR with LDO regulator achieves a temperature coefficient of 2. 1 × 10-6/ ℃ with a 1. 8 V power supply voltage and a line regulation of 4. 9 μV / V at 27 ℃. The proposed BGR with LDO regulator at 10 Hz,100 Hz,1 k Hz,10 k Hz and 100 k Hz have the PSRR of- 106. 388,- 106. 388,- 106. 38,- 105. 93 and-88. 67 d B respectively.展开更多
Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-spe...Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.展开更多
AIM：To conduct a Meta-analysis for investigating the variations in intraocular pressure（IOP）and central corneal thickness（CCT）during normal pregnancy.METHODS：We searched for clinical trials published up to Novem...AIM：To conduct a Meta-analysis for investigating the variations in intraocular pressure（IOP）and central corneal thickness（CCT）during normal pregnancy.METHODS：We searched for clinical trials published up to November 2015 without language or region restrictions in Pub Med,EMBASE,Web of Science,the Cochrane Central Register of Controlled Trials,Ovid,EBSCO,Elsevier,the Chinese Biomedicine Database,Wan Fang,CNKI,CQVIP and Google Scholar.Studies of the ocular changes observed in pregnant women were selected.The main outcomes were assessed by changes in IOP and CCT.RESULTS：Fifteen studies were included.In subgroup analyses,IOP was significantly decreased during the second MD=-1.53,95%CI（-2.19,-0.87）;P〈0.00001,and third MD=-2.91,95%CI（-3.74,-2.08）;P〈0.00001 trimesters of pregnancy.CCT was increased during the second MD=10.12,95%CI（2.01,18.22）;P=0.01,trimester of pregnancy;moreover,during the third trimester of pregnancy,the CCT displayed an increasing trend,but the difference was not significant MD=5.98,95%CI（-1.11,13.07）;P=0.1.CONCLUSION：A decrease in IOP is accompanied by an increase in CCT in the second and third trimesters of a normal pregnancy in women.展开更多
Objective: To analyze characterization of the rpoBgene mutations of Mycobacterium tuber- culosis isolated from China and to explore the association of specific mutations conferring rifampicin (RIF) resistance with Bei...Objective: To analyze characterization of the rpoBgene mutations of Mycobacterium tuber- culosis isolated from China and to explore the association of specific mutations conferring rifampicin (RIF) resistance with Beijing genotype strains. Methods: Genotypic analysis of 3479M. tuberculosis isolatesincluding 402 RIF-resistantand 3077 RIF-susceptible isolated from the na- tional drug-resistant tuberculosis baseline survey was performed. Results: DNA sequencing analysis of the 81-bp RIF resistance determining region (RRDR) of the ropB gene revealed that 98.01% of RIF-resistant strains showedrpoBgene mutation, isolates with mutations at codon rpoB531, rpoB 526 and rpoB 516 were the most frequently. Analysis of the rpoB gene of 3077 RIF-susceptible strains revealed that 98.96% of the strains had no mutation. The distribution of mutation frequency at differentcritical codons in different regions of China was statistically significant (p = 0.001). There was no significant difference in the occurrence of mutations at critical codons between the rifampicin-resistant Bei-jing and non-Beijing isolates.Conclusion: About 98% of RIF-resistant strains isolated from China carry mutations in RRDR ofrpoB gene.Mutation profiles in RIF-resistantM. tuberculosis clinical isolates are variable depending on the different geographical regionsof China. The results provide valuable information in adopting new molecular methods for diagnosis of TB in China.展开更多
In this paper,we study an Intelligent Reflecting Surface(IRS)assisted Mobile Edge Computing(MEC)system under eavesdropping threats,where the IRS is used to enhance the energy signal transmission and the offloading per...In this paper,we study an Intelligent Reflecting Surface(IRS)assisted Mobile Edge Computing(MEC)system under eavesdropping threats,where the IRS is used to enhance the energy signal transmission and the offloading performance between Wireless Devices(WDs)and the Access Point(AP).Specifically,in the proposed scheme,the AP first powers all WDs with the wireless power transfer through both direct and IRS-assisted links.Then,powered by the harvested energy,all WDs securely offload their computation tasks through the two links in the time division multiple access mode.To determine the local and offloading computational bits,we formulate an optimization problem to jointly design the IRS's phase shift and allocate the time slots constrained by the security and energy requirements.To cope with this non-convex optimization problem,we adopt semidefinite relaxations,singular value decomposition techniques,and Lagrange dual method.Moreover,we propose a dichotomy particle swarm algorithm based on the bisection method to process the overall optimization problem and improve the convergence speed.The numerical results illustrate that the proposed scheme can boost the performance of MEC and secure computation rates compared with other IRS-assisted MEC benchmark schemes.展开更多
Trifluoroacetic acid(TFA)catalyzed condensation reaction between tetraaminooxacalix[4]arene and N-alkylcarbazole-3,6-dicarbaldehyde in CH_(2)Cl2afforded a single product in 87%–89%yield.Well-defined yet undissolvable...Trifluoroacetic acid(TFA)catalyzed condensation reaction between tetraaminooxacalix[4]arene and N-alkylcarbazole-3,6-dicarbaldehyde in CH_(2)Cl2afforded a single product in 87%–89%yield.Well-defined yet undissolvable1H NMR spectra suggested formation of robust and discrete structures in solution.X-ray single crystal analysis further revealed a giant twisted double-layer chiral macrocycle in the solid state,which was formed from[4+8]condensation of the two reactants via 16 imine bonds.DFT calculations discovered that only the[4+8]twisted product is thermodynamically favorable,which accounts for its highly selective and efficient formation out of a library of many other combinations.展开更多
Abstract:Tuberculosis(TB)remains a significant global health challenge,ranking second only to COVID-19 as the leading cause of death from a single infectious agent,with 1.3 million TB-related deaths reported in 2022.T...Abstract:Tuberculosis(TB)remains a significant global health challenge,ranking second only to COVID-19 as the leading cause of death from a single infectious agent,with 1.3 million TB-related deaths reported in 2022.Treatment efficacy has been compromised by the emergence of drug-resistant strains,including rifampin-resistant TB(RR-TB),multidrug-resistant TB(MDR-TB),and extensively drug-resistant TB(XDR-TB).Although first-line drugs like isoniazid,rifampicin,pyrazinamide,and ethambutol form the cornerstone of TB therapy,the rise of resistant strains necessitates the use of second-line drugs,which often come with increased toxicity and limited accessibility.Recent advances have focused on repurposing existing compounds and developing new drugs with novel mechanisms of action.Promising agents such as second-generation bedaquiline analogs(TBAJ-587,TBAJ-876),sudapyridine(WX-081),delamanid,pretomanid,and TBI-166(pyrifazimine)have shown efficacy against resistant Mtb strains.Innovative treatment regimens like the BPaLM protocol-combining bedaquiline,pretomanid,linezolid,and moxifloxacin-offer shorter,all-oral therapies with higher cure rates.展开更多
Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if p...Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs’effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.展开更多
Combination therapy is a widely used clinical strategy to enhance treatment efficacy against solid tumors.However,the diversity of medicinal drugs and the complexity of in vivo delivery processes present significant c...Combination therapy is a widely used clinical strategy to enhance treatment efficacy against solid tumors.However,the diversity of medicinal drugs and the complexity of in vivo delivery processes present significant challenges for the rational selection and efficient delivery of drug combinations.As a proof of concept,we herein developed an omics-based high-throughput drug screening platform,pharmacotranscriptomic signature enrichment analysis(PSEA),for the prediction of drug combinations of resiquimod(R848)to improve macrophage-mediated cancer immunotherapy.By comparing the critical transcriptional signatures of R848 with chemical perturbation signatures from the LINCS database,PSEA identified mitoxantrone(MIT)as a promising candidate.We then engineered an MIT/R848 co-loaded hydrogel(MIT/R848@Gel)and tested its therapeutic effect in multiple tumor models including the MMTV-PyMT transgenic mouse tumor and VX2 rabbit tumor.Local injection of MIT/R848@Gel not only suppressed the growth of primary tumors but also potently inhibited tumor recurrence and metastasis by eliciting durable and robust systemic antitumor immune responses,resulting in long-term remission in a high percentage of animals.Transcriptional and flow cytometry results indicated that MIT/R848@Gel remarkably reprogrammed immunosuppressive macrophages toward an antitumor phenotype and effectively activated the antitumor effect of cytotoxic T cells.This study establishes a novel framework integrating omics-driven drug discovery with localized combination therapy for enhanced cancer immunotherapy.展开更多
The discovery of fluorescence materials with an inverted singlet-triplet(IST)energy gap,where the singlet excited state(S_(1))lies below the triplet excited state(T_(1)),mark a transformative advancement in organic li...The discovery of fluorescence materials with an inverted singlet-triplet(IST)energy gap,where the singlet excited state(S_(1))lies below the triplet excited state(T_(1)),mark a transformative advancement in organic light-emitting diodes(OLEDs)technology.However,designing the potential IST emitters are greatly challenging,and their IST energy gap,arising from double electron excitation,can only be accurately described by time-consuming post-Hartree-Fock(HF)methods,which blocks large-scale high-throughput screening speed.Here,we develop a four-orbital model to elucidate detailly the roles of double excitations in the IST formation,and establish two molecular descriptors(K_(S)and O_(D))based on exchange integral and molecular orbital energy.By these descriptors,we rapidly identify 41 IST candidates out of 3,486 molecules.The descriptors-aided approach achieves a screening success rate of 90%and reduces computational costs by 13 times compared to full post-HF calculations.Importantly,wepredicted a series of excellent non-traditional near-infrared IST emitters from a dataset of 1028 compounds with emission wavelengths ranging from 852.2 to 1002.3 nm,which open new avenues for designing highly efficient near-infrared OLED materials.展开更多
Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zh...Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.展开更多
Background:China is one of 22 countries with a high tuberculosis(TB)burden in the world.Healthcare workers(HCWs)have a high risk of contracting Mycobacterium tuberculosis infection due to insufficient infection contro...Background:China is one of 22 countries with a high tuberculosis(TB)burden in the world.Healthcare workers(HCWs)have a high risk of contracting Mycobacterium tuberculosis infection due to insufficient infection control practices.We conducted a cross-sectional study to explore the prevalence of TB and its associated risk factors among HCWs in Chinese TB facilities.Methods:Two hundred and forty-one TB facilities employing a total of 9663 HCWs were selected from 12 provinces in China to represent healthcare settings at the provincial,prefectural,and county levels.Structured questionnaires were used to collect information on TB infection control practices and HCWs in those facilities.Data was double entered into EpiData 3.1;TB prevalence and associated risk factors were analyzed using SPSS 21.0 with bivariate and multivariate regression models.Results:The results showed that 71 HCWs had been diagnosed with TB,accounting for a prevalence of 760/100000.The multivariate analysis showed that associated risk factors included belonging to the age group of 51 years and above(aOR:6.17,95%CI:1.35-28.28),being a nurse(aOR=3.09,95%CI:1.15-8.32),implementation of 0-9 items of management measures(aOR=2.57,95%CI:1.37-4.80),and implementation of 0-1 items of ventilation measures(aOR=2.42,95%CI:1.31-4.47).Conclusion:This was the first national large sampling survey on TB prevalence among HCWs in China.It was found that the implementation of TB infection control practices in some facilities was poor.The TB prevalence in HCWs was higher than that in the general population.Therefore,TB infection control practices in Chinese medical facilities should be strengthened.展开更多
Secondary xylem development has long been recognized as a typical case of programmed cell death （PCD） in plants. During PCD, the degradation of genomic DNA is catalyzed by endonucleases. However, to date, no endonuc...Secondary xylem development has long been recognized as a typical case of programmed cell death （PCD） in plants. During PCD, the degradation of genomic DNA is catalyzed by endonucleases. However, to date, no endonuclease has been shown to participate in secondary xylem development. Two novel Ca^2＋-dependent DNase genes, EuCaN1 and EuCaN2, were identified from the differentiating secondary xylem of the tree Eucommia ulmoides Oliv., their functions were studied by DNase activity assay, in situ hybridization, protein immunolocalization and virus-induced gene silencing experiments. Full-length cDNAs of EuCaN1 and EuCaN2 contained an open reading frame of 987 bp, encoding two proteins of 328 amino acids with SNase-like functional domains. The genomic DNA sequence for EuCaN1 had no introns, while EuCaN2 had 8 introns. EuCaN1 and EuCaN2 digested ssDNA and dsDNA with Ca^2＋-dependence at neutral pH. Their expression was confined to differentiating secondary xylem cells and the proteins were localized in the nucleus. Their activity dynamics was closely correlated with secondary xylem development. Secondary xylem cell differentiation is influenced by RNAi of endonuclease genes. The results provide evidence that the Ca^2＋-dependent DNases are involved in secondary xylem development.展开更多
基金Supported by the Scientific Research Fund of Tai’an Science and Technology Agency,No.2019NS180.
文摘Triple negative breast cancer(TNBC)is an exceptionally aggressive subtype of breast cancer with a poor prognosis.TNBC patients have limited treatment options beyond conventional chemotherapy,and they face significant challenges associated with disease recurrence and resistance to chemotherapy.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway plays a pivotal role in cell proliferation,growth,metabolism,and survival.Its aberrant activation is closely linked to the development and progression of TNBC,as well as treatment response and drug resistance.Currently,numerous targeted drugs specifically inhibiting this signaling pathway are being developed and undergoing clinical trials.These include inhibitors targeting PI3K,AKT,or mTOR individually,as well as dual-target or multi-target inhibitors simultaneously targeting different components of this pathway.Encouragingly,some inhibitors have demonstrated promising potential in clinical trials.This review delves into the therapeutic potential of the PI3K/AKT/mTOR signaling pathway for TNBC and explores prospects for drug discovery.
基金supported by the Peking University Medicine Fund of Fostering Young Scholars'Scientific&Technological Innovation[grant number BMU2024YFJHPY014]the Fundamental Research Funds for the Central Universities+1 种基金the Key Clinical Projects of Peking University Third Hospital[grant number BYSYZD2022014]the Capital’s Funds for Health Improvement and Research[grant number 2022-2G-40910]。
文摘Objective Cigarette smoking exacerbates the progression of pulmonary tuberculosis(TB).The role of tertiary lymphoid structures(TLS)in chronic lung diseases has gained attention;however,it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS.This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB.Methods Lung tissues from 36 male patients(18 smokers and 18 non-smokers)who underwent surgical resection for pulmonary TB were included in this study.Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS,and chest computed tomography(CT)was used to assess the severity of lung lesions.The correlation between the TLS quantity and TB lesion severity scores was analyzed.The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers.Results Smoker patients with TB had significantly higher TLS than non-smokers(P<0.001).The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT(parenchyma:r=0.5767;peribronchial:r=0.7373;both P<0.001).Immunohistochemical analysis showed increased B cells,T cells,and C-X-C motif chemokine ligand 13(CXCL13)expression in smoker patients with TB(P<0.001).Conclusion Smoker TB patients exhibited increased pulmonary TLS,which was associated with exacerbated lung lesions on chest CT,suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
基金2023 Guangdong Provincial Educational Science Planning Project(Higher Education Special Program)“Research on the Talent Cultivation Path of Vocational Undergraduate Programs in Finance,Economics and Trade Based on Digital Transformation”(2023GXJK653)。
文摘With the development of the current era,China’s Internet and computer technologies are constantly updated and improved.Under the application of information technology,great changes have taken place in the financial management work of schools.At present,the content of school financial management work is constantly increasing.In order to meet the needs of school management,it is necessary to improve the level of financial management,strengthen the informatization construction of financial management,so as to realize the modernization of school financial management and improve the efficiency of financial management.Big data technology and information technology can realize the rapid collection and preprocessing of information,achieve in-depth mining of data value,assist staff in quickly identifying problems in their work,and further improve work efficiency.Based on this,this paper conducts in-depth analysis and research on the informatization construction of financial management in colleges and universities on the basis of big data,for reference.
基金financially supported by National Natural Science Foundation of China(No.61874137)。
文摘A recent progress in new emerging two-dimensional(2 D)materials has provided promising opportunity for gas sensing in ultra-low detectable concentration.In this work,we have demonstrated a flexible NO2 gas sensor with porous structure graphene on polyethylene terephthalate substrates operating at room temperature.The gas sensor exhibited good performance with response of 1.2%and a fast response time within 30 s after exposure to50×10^-9 NO2 gas.As porous structure of graphene increased the surface area,the sensor showed high sensitivity of ppb level for NO2 detection.Au nanoparticles were decorated on the surface of the porous structure graphene skeleton,resulting in an incensement of response compared with pristine graphene.Au nanoparticles-decorated graphene exhibits not only better sensitivity(1.5-1.6 times larger than pristine graphene)for NO2 gas detection,but also fast response.The sensor was found to be robust and sensitive under the cycling bending test,which could also be ascribed to the merits of graphene.This porous structure graphene-based gas sensor is expected to enable a simple and inexpensive flexible gas sensing platform.
基金supported by the National Natural Science Foundation of China(Nos.10672108 and 10632020)the key project of the Ministry of Education of China(No.206014).
文摘This paper is concerned with the dynamic behaviors of wave propagation in layered periodic composites consisting of piezoelectric and piezomagnetic phases. The dispersion relations of Lamb waves axe derived. Dispersion curves and displacement fields are calculated with different piezoelectric volume fractions. Numerical results for BaTiO3/CoFe2O4 composites show that the dispersion curves resemble the symmetric Lamb waves in a plate. Exchange between the longitudinal （i.e. thickness） mode and coupled mode takes place at the crossover point between dispersion curves of the first two branches. With the increase of BaTiO3 volume fraction, the crossover point appears at a lower wave number and wave velocity is higher. These findings are useful for magnetoelectric transducer applications.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1511300)the National Natural Science Foundation of China(Grant No.U21A20447 and 61971079)+2 种基金the Basic Research and Frontier Exploration Project of Chongqing (Grant No.cstc2019jcyj-msxmX0666)the Innovative Group Project of the National Natural Science Foundation of Chongqing (Grant No.cstc2020jcyj-cxttX0002)the Regional Creative Cooperation Program of Sichuan (2020YFQ0025).
文摘The Multiple-Input Multiple-Output(MIMO)Non-Orthogonal Multiple Access(NOMA)based on Spatial Modulation(SM-MIMO-NOMA)system has been proposed to achieve better spectral efficiency with reduced radio frequency chains comparing to the traditional MIMO-NOMA system.To improve the performance of SM-MIMO-NOMA systems,we extend them to generalized spatial modulation scenarios while maintaining moderate complexity and fairness.In this paper,system spectral efficiency and transmission quality improvements are proposed by investigating a sum-rate maximization resource allocation problem that is subject to the total transmitted power,user grouping,and resource block constraints.To solve this non-convex and difficult problem,a graph-based user grouping strategy is proposed initially to maximize the mutual gains of intragroup users.An auxiliary-variable approach is then adopted to transform the power allocation subproblem into a convex one.Simulation results demonstrate that the proposed algorithm has better performance in terms of bit error rate and sum rates.
基金Sponsored by the National Natural Science Foundation of China(Grant No.61471075)the 2013 Program for Innovation Team Building at Institutions of Higher Education in Chongqing(The Innovation Team of Smart Medical System and Key Technology)
文摘A high-PSRR high-order curvature-compensated CMOS bandgap voltage reference( BGR),which has the performances of high power supply rejection ratio( PSRR) and low temperature coefficient,is designed in SMIC 0. 18 μm CMOS process. Compared to the conventional curvature-compensated BGR which adopted a piecewise-linear current,the temperature characterize of the proposed BGR is effectively improved by adopting two kinds of current including a piecewise-linear current and a current proportional 1. 5 party to the absolute temperature T. By adopting a low dropout( LDO) regulator whose output voltage is the operating supply voltage of the proposed BGR core circuit instead of power supply voltage VDD,the proposed BGR with LDO regulator achieves a well PSRR performance than the BGR without LDO regulator. Simulation results show that the proposed BGR with LDO regulator achieves a temperature coefficient of 2. 1 × 10-6/ ℃ with a 1. 8 V power supply voltage and a line regulation of 4. 9 μV / V at 27 ℃. The proposed BGR with LDO regulator at 10 Hz,100 Hz,1 k Hz,10 k Hz and 100 k Hz have the PSRR of- 106. 388,- 106. 388,- 106. 38,- 105. 93 and-88. 67 d B respectively.
基金supported by the Beijing Municipal Science&Technology Commission(Z191100006619077).
文摘Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.
基金Supported by the National Nature Science Foundation of China(No.81570841)
文摘AIM：To conduct a Meta-analysis for investigating the variations in intraocular pressure（IOP）and central corneal thickness（CCT）during normal pregnancy.METHODS：We searched for clinical trials published up to November 2015 without language or region restrictions in Pub Med,EMBASE,Web of Science,the Cochrane Central Register of Controlled Trials,Ovid,EBSCO,Elsevier,the Chinese Biomedicine Database,Wan Fang,CNKI,CQVIP and Google Scholar.Studies of the ocular changes observed in pregnant women were selected.The main outcomes were assessed by changes in IOP and CCT.RESULTS：Fifteen studies were included.In subgroup analyses,IOP was significantly decreased during the second MD=-1.53,95%CI（-2.19,-0.87）;P〈0.00001,and third MD=-2.91,95%CI（-3.74,-2.08）;P〈0.00001 trimesters of pregnancy.CCT was increased during the second MD=10.12,95%CI（2.01,18.22）;P=0.01,trimester of pregnancy;moreover,during the third trimester of pregnancy,the CCT displayed an increasing trend,but the difference was not significant MD=5.98,95%CI（-1.11,13.07）;P=0.1.CONCLUSION：A decrease in IOP is accompanied by an increase in CCT in the second and third trimesters of a normal pregnancy in women.
文摘Objective: To analyze characterization of the rpoBgene mutations of Mycobacterium tuber- culosis isolated from China and to explore the association of specific mutations conferring rifampicin (RIF) resistance with Beijing genotype strains. Methods: Genotypic analysis of 3479M. tuberculosis isolatesincluding 402 RIF-resistantand 3077 RIF-susceptible isolated from the na- tional drug-resistant tuberculosis baseline survey was performed. Results: DNA sequencing analysis of the 81-bp RIF resistance determining region (RRDR) of the ropB gene revealed that 98.01% of RIF-resistant strains showedrpoBgene mutation, isolates with mutations at codon rpoB531, rpoB 526 and rpoB 516 were the most frequently. Analysis of the rpoB gene of 3077 RIF-susceptible strains revealed that 98.96% of the strains had no mutation. The distribution of mutation frequency at differentcritical codons in different regions of China was statistically significant (p = 0.001). There was no significant difference in the occurrence of mutations at critical codons between the rifampicin-resistant Bei-jing and non-Beijing isolates.Conclusion: About 98% of RIF-resistant strains isolated from China carry mutations in RRDR ofrpoB gene.Mutation profiles in RIF-resistantM. tuberculosis clinical isolates are variable depending on the different geographical regionsof China. The results provide valuable information in adopting new molecular methods for diagnosis of TB in China.
基金supported in part by the National Natural Science Foundation of China under Grant 62271399 and 62206221in part by the Key Research and Development Program of Shaanxi Province under Grant 2022KW-07+1 种基金in part by National Key Research and Development Program of China under Grant 2020YFB1807003in part by the Shanghai Sailing Program under Grant 20YF1416700。
文摘In this paper,we study an Intelligent Reflecting Surface(IRS)assisted Mobile Edge Computing(MEC)system under eavesdropping threats,where the IRS is used to enhance the energy signal transmission and the offloading performance between Wireless Devices(WDs)and the Access Point(AP).Specifically,in the proposed scheme,the AP first powers all WDs with the wireless power transfer through both direct and IRS-assisted links.Then,powered by the harvested energy,all WDs securely offload their computation tasks through the two links in the time division multiple access mode.To determine the local and offloading computational bits,we formulate an optimization problem to jointly design the IRS's phase shift and allocate the time slots constrained by the security and energy requirements.To cope with this non-convex optimization problem,we adopt semidefinite relaxations,singular value decomposition techniques,and Lagrange dual method.Moreover,we propose a dichotomy particle swarm algorithm based on the bisection method to process the overall optimization problem and improve the convergence speed.The numerical results illustrate that the proposed scheme can boost the performance of MEC and secure computation rates compared with other IRS-assisted MEC benchmark schemes.
基金supported by the National Natural Science Foundation of China(Nos.21971223 and 21772178)。
文摘Trifluoroacetic acid(TFA)catalyzed condensation reaction between tetraaminooxacalix[4]arene and N-alkylcarbazole-3,6-dicarbaldehyde in CH_(2)Cl2afforded a single product in 87%–89%yield.Well-defined yet undissolvable1H NMR spectra suggested formation of robust and discrete structures in solution.X-ray single crystal analysis further revealed a giant twisted double-layer chiral macrocycle in the solid state,which was formed from[4+8]condensation of the two reactants via 16 imine bonds.DFT calculations discovered that only the[4+8]twisted product is thermodynamically favorable,which accounts for its highly selective and efficient formation out of a library of many other combinations.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC2302903).
文摘Abstract:Tuberculosis(TB)remains a significant global health challenge,ranking second only to COVID-19 as the leading cause of death from a single infectious agent,with 1.3 million TB-related deaths reported in 2022.Treatment efficacy has been compromised by the emergence of drug-resistant strains,including rifampin-resistant TB(RR-TB),multidrug-resistant TB(MDR-TB),and extensively drug-resistant TB(XDR-TB).Although first-line drugs like isoniazid,rifampicin,pyrazinamide,and ethambutol form the cornerstone of TB therapy,the rise of resistant strains necessitates the use of second-line drugs,which often come with increased toxicity and limited accessibility.Recent advances have focused on repurposing existing compounds and developing new drugs with novel mechanisms of action.Promising agents such as second-generation bedaquiline analogs(TBAJ-587,TBAJ-876),sudapyridine(WX-081),delamanid,pretomanid,and TBI-166(pyrifazimine)have shown efficacy against resistant Mtb strains.Innovative treatment regimens like the BPaLM protocol-combining bedaquiline,pretomanid,linezolid,and moxifloxacin-offer shorter,all-oral therapies with higher cure rates.
基金supported by the Beijing Hospitals Authority Clinical Medicine Development of Special Funding(ZYLX202122)Beijing Key Clinical Specialty Project(20201214)+1 种基金Tongzhou Lianggao Talents Project(No.YHLJ202005)Beijing Nova Program(20220484169&20230484295).
文摘Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs’effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.
基金supported by the National Key R&D Program of China(2022YFC3401400)the National Natural Science Foundation of China(22477031,52173122,82372055,and 22577032)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515120028)Guangzhou Science and Technology Planning Project(2024A04J3631)the Guangdong Provincial Natural Science Foundation for Distinguished Young Scholars(2023B1515020042 and 2023B1515020062)the China Postdoctoral Science Foundation(2024M760604).
文摘Combination therapy is a widely used clinical strategy to enhance treatment efficacy against solid tumors.However,the diversity of medicinal drugs and the complexity of in vivo delivery processes present significant challenges for the rational selection and efficient delivery of drug combinations.As a proof of concept,we herein developed an omics-based high-throughput drug screening platform,pharmacotranscriptomic signature enrichment analysis(PSEA),for the prediction of drug combinations of resiquimod(R848)to improve macrophage-mediated cancer immunotherapy.By comparing the critical transcriptional signatures of R848 with chemical perturbation signatures from the LINCS database,PSEA identified mitoxantrone(MIT)as a promising candidate.We then engineered an MIT/R848 co-loaded hydrogel(MIT/R848@Gel)and tested its therapeutic effect in multiple tumor models including the MMTV-PyMT transgenic mouse tumor and VX2 rabbit tumor.Local injection of MIT/R848@Gel not only suppressed the growth of primary tumors but also potently inhibited tumor recurrence and metastasis by eliciting durable and robust systemic antitumor immune responses,resulting in long-term remission in a high percentage of animals.Transcriptional and flow cytometry results indicated that MIT/R848@Gel remarkably reprogrammed immunosuppressive macrophages toward an antitumor phenotype and effectively activated the antitumor effect of cytotoxic T cells.This study establishes a novel framework integrating omics-driven drug discovery with localized combination therapy for enhanced cancer immunotherapy.
基金support from the National Natural Science Foundation of China(Grant Nos.22325305 and 22273105)the Strategic Priority Research Program of Sciences(XDB0520103)+1 种基金National Key R&D Program of China(2024YFB3614300)the Fundamental Research Funds for the Central Universities(Grant Nos.E2E40307X2 and E2ET0309X2).We gratefully acknowledge WQ&UCAS Research Academy Intelligent Computing Center(WRA-ICC)for providing computation facilities.
文摘The discovery of fluorescence materials with an inverted singlet-triplet(IST)energy gap,where the singlet excited state(S_(1))lies below the triplet excited state(T_(1)),mark a transformative advancement in organic light-emitting diodes(OLEDs)technology.However,designing the potential IST emitters are greatly challenging,and their IST energy gap,arising from double electron excitation,can only be accurately described by time-consuming post-Hartree-Fock(HF)methods,which blocks large-scale high-throughput screening speed.Here,we develop a four-orbital model to elucidate detailly the roles of double excitations in the IST formation,and establish two molecular descriptors(K_(S)and O_(D))based on exchange integral and molecular orbital energy.By these descriptors,we rapidly identify 41 IST candidates out of 3,486 molecules.The descriptors-aided approach achieves a screening success rate of 90%and reduces computational costs by 13 times compared to full post-HF calculations.Importantly,wepredicted a series of excellent non-traditional near-infrared IST emitters from a dataset of 1028 compounds with emission wavelengths ranging from 852.2 to 1002.3 nm,which open new avenues for designing highly efficient near-infrared OLED materials.
基金supported by the National Natural Science Foundation of China(Nos.81874368 and 81630100)the Beijing Nova Program(No.Z181100006218001)+2 种基金the National Key Technology R&D Program(No.2015ZX 09501-004-001-008)the National Key R&D Program of China(No.2018YFC1707000)the National TCM Industry Science and Technology Program(No.201507004-4-2).
文摘Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.
基金Funding was obtained from the Global Fund Project(TB12-0010)the Research Project and Achievement Management of Department of Science and Technology of the China CDC.The contents of this publication are the sole responsibility of the authors.
文摘Background:China is one of 22 countries with a high tuberculosis(TB)burden in the world.Healthcare workers(HCWs)have a high risk of contracting Mycobacterium tuberculosis infection due to insufficient infection control practices.We conducted a cross-sectional study to explore the prevalence of TB and its associated risk factors among HCWs in Chinese TB facilities.Methods:Two hundred and forty-one TB facilities employing a total of 9663 HCWs were selected from 12 provinces in China to represent healthcare settings at the provincial,prefectural,and county levels.Structured questionnaires were used to collect information on TB infection control practices and HCWs in those facilities.Data was double entered into EpiData 3.1;TB prevalence and associated risk factors were analyzed using SPSS 21.0 with bivariate and multivariate regression models.Results:The results showed that 71 HCWs had been diagnosed with TB,accounting for a prevalence of 760/100000.The multivariate analysis showed that associated risk factors included belonging to the age group of 51 years and above(aOR:6.17,95%CI:1.35-28.28),being a nurse(aOR=3.09,95%CI:1.15-8.32),implementation of 0-9 items of management measures(aOR=2.57,95%CI:1.37-4.80),and implementation of 0-1 items of ventilation measures(aOR=2.42,95%CI:1.31-4.47).Conclusion:This was the first national large sampling survey on TB prevalence among HCWs in China.It was found that the implementation of TB infection control practices in some facilities was poor.The TB prevalence in HCWs was higher than that in the general population.Therefore,TB infection control practices in Chinese medical facilities should be strengthened.
基金supported by the National Basic Research Program of China (2012CB114500)the National Natural Science Foundation of China (31070156)
文摘Secondary xylem development has long been recognized as a typical case of programmed cell death （PCD） in plants. During PCD, the degradation of genomic DNA is catalyzed by endonucleases. However, to date, no endonuclease has been shown to participate in secondary xylem development. Two novel Ca^2＋-dependent DNase genes, EuCaN1 and EuCaN2, were identified from the differentiating secondary xylem of the tree Eucommia ulmoides Oliv., their functions were studied by DNase activity assay, in situ hybridization, protein immunolocalization and virus-induced gene silencing experiments. Full-length cDNAs of EuCaN1 and EuCaN2 contained an open reading frame of 987 bp, encoding two proteins of 328 amino acids with SNase-like functional domains. The genomic DNA sequence for EuCaN1 had no introns, while EuCaN2 had 8 introns. EuCaN1 and EuCaN2 digested ssDNA and dsDNA with Ca^2＋-dependence at neutral pH. Their expression was confined to differentiating secondary xylem cells and the proteins were localized in the nucleus. Their activity dynamics was closely correlated with secondary xylem development. Secondary xylem cell differentiation is influenced by RNAi of endonuclease genes. The results provide evidence that the Ca^2＋-dependent DNases are involved in secondary xylem development.
