Stabilizing and Activating Active Sites: 1T-MoS2 Supported Pd Single Atoms for Efficient Hydrogen Evolution Reaction.

Metallic 1T-MoS2 with high intrinsic electronic conductivity performs Pt-like catalytic activity for hydrogen evolution reaction (HER). However, obtaining pure 1T-MoS2 is challenging due to its high formation energy and metastable properties. Herein, an in situ SO4 2--anchoring strategy is reported to synthesize a thin layer of 1T-MoS2 loaded on commercial carbon. Single Pd atoms, constituting a substantial loading of 7.2 wt%, are then immobilized on the 1T-phase MoS2 via Pd─S bonds to modulate the electronic structure and ensure a stable active phase. The resulting Pd1/1T-MoS2/C catalyst exhibits superior HER performance, featuring a low overpotential of 53 mV at the current density of 10 mA cm-2, a small Tafel slope of 37 mV dec-1, and minimal charge transfer resistance in alkaline electrolyte. Moreover, the catalyst also demonstrates efficacy in acid and neutral electrolytes. Atomic structural characterization and theoretical calculations reveal that the high activity of Pd1/1T-MoS2/C is attributed to the near-zero hydrogen adsorption energy of the activated sulfur sites on the two adjacent shells of atomic Pd.

Nondestructive Direct Patterning of Both Hole Transport and Emissive Layers for Pixelated Quantum-Dot Light-Emitting Diodes.

Considering the increasing demand for high-resolution light-emitting diodes (LEDs), it is important that direct fine patterning technologies for LEDs be developed, especially for quantum-dot LEDs (QLEDs). Traditionally, the patterning of QLEDs relies on resin-based photolithography techniques, requiring multiple steps and causing performance deterioration. Nondestructive direct patterning may provide an easy and stepwise method to achieve fine-pixelated units in QLEDs. In this study, two isomeric tridentate cross-linkers (X8/X9) are presented and can be blended into the hole transport layer (HTL) and the emissive layer (EML) of QLEDs. Because of their photosensitivity, the in situ cross-linking process can be efficiently triggered by ultraviolet irradiation, affording high solvent resistance and nondestructive direct patterning of the layers. Red QLEDs using the cross-linked HTL demonstrate an impressive external quantum efficiency of up to 22.45%. Through lithographic patterning enabled by X9, line patterns of HTL and EML films exhibit widths as narrow as 2 and 4 µm, respectively. Leveraging the patterned HTL and EML, we show the successful fabrication of pixelated QLED devices with an area size of 3 × 3 mm2, alongside the successful production of dual-color pixelated QLED devices. These findings showcase the promising potential of direct patterning facilitated by engineered cross-linkers for the cost-effective fabrication of pixelated QLED displays.

The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis.

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

Pan-cancer analysis of CDKN2A alterations identifies a subset of gastric cancer with a cold tumor immune microenvironment.

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.

Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

Contrastive and uncertainty-aware nuclei segmentation and classification.

Nuclei segmentation and classification play a crucial role in pathology diagnosis, enabling pathologists to analyze cellular characteristics accurately. Overlapping cluster nuclei, misdetection of small-scale nuclei, and pleomorphic nuclei-induced misclassification have always been major challenges in the nuclei segmentation and classification tasks. To this end, we introduce an auxiliary task of nuclei boundary-guided contrastive learning to enhance the representativeness and discriminative power of visual features, particularly for addressing the challenge posed by the unclear contours of adherent nuclei and small nuclei. In addition, misclassifications resulting from pleomorphic nuclei often exhibit low classification confidence, indicating a high level of uncertainty. To mitigate misclassification, we capitalize on the characteristic clustering of similar cells to propose a locality-aware class embedding module, offering a regional perspective to capture category information. Moreover, we address uncertain classification in densely aggregated nuclei by designing a top-k uncertainty attention module that leverages deep features to enhance shallow features, thereby improving the learning of contextual semantic information. We demonstrate that the proposed network outperforms the off-the-shelf methods in both nuclei segmentation and classification experiments, achieving the state-of-the-art performance.

Invoking Interfacial Engineering Boosts Structural Stability Empowering Exceptional Cyclability of Ni-Rich Cathode.

The cycling stability of LiNi0.8Co0.1Mn0.1O2 under high voltages is hindered by the occurrence of hybrid anion- and cation-redox processes, leading to oxygen escape and uncontrolled phase collapse. In this study, we propose an interfacial engineering strategy involving a straightforward mechanical ball milling and low-temperature calcination, employing a Se-doped and FeSe2&Fe2O3-modified approach to design a stable Ni-rich cathode. Se2- are selectively adsorbed within oxygen vacancies to form O-TM-Se bond, effectively stabilizing lattice oxygen, and preventing structural distortion. Simultaneously, the Se-NCM811//FeSe2//Fe2O3 self-assembled electric field is activated, improving interfacial charge transfer and coupling. Furthermore, FeSe2 accelerates Li+ diffusion and reacts with oxygen to form Fe2O3 and SeO2. The Fe2O3 coating mitigates HF erosion and acts as an electrostatic shield layer, limiting the outward migration of oxygen anions. Impressively, the modified materials exhibit significantly improved electrochemical performance, with a capacity retention of 79.7% after 500 cycles at 1C under 4.5 V. Furthermore, it provides an extraordinary capacity retention of 94.6% in 3 - 4.25 V after 550 cycles in pouch-type full battery. This dual-modification approach demonstrates its feasibility and opens new perspectives for the development of stable lithium-ion batteries operating at high voltages. This article is protected by copyright. All rights reserved.

Highly diverse RNA viruses and phage sequences concealed within birds.

The diversity of birds in most parts of the world is very high, and thus, they may carry different types of highly differentiated and unknown viruses. Thanks to advanced sequencing technologies, studies on the diversity of bird-associated viruses have increased over the past few years. In this study, a large-scale viral metagenomics survey was performed on cloacal swabs of 2,990 birds from nine provinces of the Chinese mainland. To detect undescribed RNA viruses in birds, more than 1,800 sequences sharing relatively low (<60%) amino acid sequence identity with the best match in the GenBank database were screened. Potentially novel viruses related to vertebrates have been identified, and several potential recombination signals were found. Additionally, hundreds of RNA viral sequences related to plants, fungi, and insects were detected, including previously unknown viruses. Furthermore, we investigated the novelty, functionality, and classification of the phages examined in this study. These viruses occupied topological positions on the evolutionary trees to a certain extent and might form novel putative families, genera, or species, thus providing information to fill the phylogenetic gaps of related viruses. These findings provided new insights into bird-associated viruses, but the interactions among these viruses remain unknown and require further investigation.IMPORTANCEStudying the diversity of RNA viruses in birds and mammals is crucial due to their potential impact on human health and the global ecosystem. Many RNA viruses, such as influenza and coronaviruses, have been shown to cross the species barrier and cause zoonotic diseases. In this metagenomics study involving 2,990 birds from at least 82 species, we identified over 1,800 RNA sequences with distant relationships to known viruses, some of which are rare in birds. The study highlights the scope and diversity of RNA viruses in birds, providing data to predict disease risks and monitor potential viral threats to wildlife, livestock, and human health. This information can aid in the development of strategies for disease prevention and control.

An Elastomeric Lithium-Conducting Interlayer for High-Performance LATP-Based Lithium Metal Batteries.

In response to the critical challenges of interfacial impedance and volumetric changes in Li(1+x)AlxTi(2­x)(PO4)3 (LATP)-based lithium metal batteries, an elastomeric lithium-conducting interlayer fabricates from fluorinated hydrogenated nitrile butadiene rubber (F-HNBR) matrix is introduced herein. Owing to the vulcanization, vapor-phase fluorination, and plasticization processes, the lithium-conducting interlayer exhibits a high elasticity of 423%, exceptional fatigue resistance (10 000 compression cycles), superior ionic conductivity of 6.3 × 10-4 S cm-1, and favorable lithiophilicity, rendering it an ideal buffer layer. By integrating the F-HNBR interlayer, the LATP-based lithium symmetric cells demonstrate an extended cycle life of up to 1600 h at 0.1 mA cm-2 and can also endure deep charge/discharge cycles (0.5 mAh cm-2) for the same duration. Furthermore, the corresponding lithium metal full cells achieve 500 cycles at 0.5 C with 98.3% capacity retention and enable a high-mass-loading cathode of 11.1 mg cm-2 to operate at room temperature.

Graphene-integrated microring cavity for electronically controlled molecular fingerprinting.

Microring cavities supporting whispering-gallery modes (WGMs) have an exceptionally high quality factor (Q) and a small mode volume, greatly improving the interaction between light and matter, which has attracted great attention in various microscale/nanoscale photonic devices and potential applications. Recently, two-dimensional van der Waals (vdW) materials such as graphene have emerged as a potential platform for next-generation biosensing by enabling the confinement of light fields at the nanoscale. Here, we propose what we believe to be a novel approach to achieve molecular fingerprint retrieval by integrating graphene into a microring cavity and conducting numerical simulations using the finite-difference time-domain (FDTD) method. The hybrid cavity exhibits high-quality WGMs with a high Q factor of up to 800. Moreover, the resonant wavelength can be electronically controlled through modulation of graphene's Fermi level, enabling coverage of the entire free spectral range at infrared frequencies. By depositing a thin layer of biomolecular material (e.g., CBP) onto the surface of our hybrid cavity, we are able to accurately read out the absorption spectrum at multiple spectral points, thereby achieving broadband fingerprint retrieval for the targeted biomolecule. Our results pave the way for highly sensitive, chip-integrated, miniaturized, and electrically modulated infrared spectroscopy biosensing.

Antibody drugs targeting SARS-CoV-2: Time for a rethink?

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) heavily burdens human health. Multiple neutralizing antibodies (nAbs) have been issued for emergency use or tested for treating infected patients in the clinic. However, SARS-CoV-2 variants of concern (VOC) carrying mutations reduce the effectiveness of nAbs by preventing neutralization. Uncoding the mutation profile and immune evasion mechanism of SARS-CoV-2 can improve the outcome of Ab-mediated therapies. In this review, we first outline the development status of anti-SARS-CoV-2 Ab drugs and provide an overview of SARS-CoV-2 variants and their prevalence. We next focus on the failure causes of anti-SARS-CoV-2 Ab drugs and rethink the design strategy for developing new Ab drugs against COVID-19. This review provides updated information for the development of therapeutic Ab drugs against SARS-CoV-2 variants.

Gallic Acid Alleviates Psoriasis Keratinization and Inflammation by Regulating BRD4 Expression.

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.

Low expression of Notch1 may be associated with acute myocardial infarction.

Background: The transmembrane protein Notch1 is associated with cell growth, development, differentiation, proliferation, apoptosis, adhesion, and the epithelial mesenchymal transition. Proteomics, as a research method, uses a series of sequencing techniques to study the composition, expression levels, and modifications of proteins. Here, the association between Notch1 and acute myocardial infarction (AMI) was investigated using proteomics, to assess the possibility of using Notch1 as a biomarker for the disease. Methods: Fifty-five eligible patients with AMI and 74 with chronic coronary syndrome (CCS) were enrolled, representing the experimental and control groups, respectively. The mRNA levels were assessed using RT-qPCR and proteins were measured using ELISA, and the results were compared and analyzed. Results: Notch1 mRNA levels were 0.52 times higher in the peripheral blood mononuclear cells of the AMI group relative to the CCS group (p < 0.05) while Notch1 protein levels were 0.63 times higher in peripheral blood plasma in AMI patients (p < 0.05). Notch1 levels were not associated with older age, hypertension, smoking, high abdominal-blood glucose, high total cholesterol, and high LDL in AMI. Logistic regression indicated associations between AMI and reduced Notch1 expression, hypertension, smoking, and high fasting glucose. Conclusions: Notch1 expression was reduced in the peripheral blood of patients with AMI relative to those with CCS. The low expression of Notch1 was found to be an independent risk factor for AMI and may thus be an indicator of the disease.

Distinct time trends in colorectal cancer incidence in countries with SDI levels from 1990 to 2019: an age-period-cohort analysis for the Global Burden of Disease 2019 study.

Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years. Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening. Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable. Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions.

Atomic engineering of two-dimensional materials via liquid metals.

Two-dimensional (2D) materials, known for their distinctive electronic, mechanical, and thermal properties, have attracted considerable attention. The precise atomic-scale synthesis of 2D materials opens up new frontiers in nanotechnology, presenting novel opportunities for material design and property control but remains challenging due to the high expense of single-crystal solid metal catalysts. Liquid metals, with their fluidity, ductility, dynamic surface, and isotropy, have significantly enhanced the catalytic processes crucial for synthesizing 2D materials, including decomposition, diffusion, and nucleation, thus presenting an unprecedented precise control over material structures and properties. Besides, the emergence of liquid alloy makes the creation of diverse heterostructures possible, offering a new dimension for atomic engineering. Significant achievements have been made in this field encompassing defect-free preparation, large-area self-aligned array, phase engineering, heterostructures, etc. This review systematically summarizes these contributions from the aspects of fundamental synthesis methods, liquid catalyst selection, resulting 2D materials, and atomic engineering. Moreover, the review sheds light on the outlook and challenges in this evolving field, providing a valuable resource for deeply understanding this field. The emergence of liquid metals has undoubtedly revolutionized the traditional nanotechnology for preparing 2D materials on solid metal catalysts, offering flexible possibilities for the advancement of next-generation electronics.

Iron metabolism and arthritis: Exploring connections and therapeutic avenues.

ABSTRACT: Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Advances in antitumor application of ROS enzyme-mimetic catalysts.

The rapid growth of research on enzyme-mimetic catalysts (Enz-Cats) is expected to promote further advances in nanomedicine for biological detection, diagnosis and treatment of disease, especially tumors. ROS-based nanomedicines present fascinating potential in antitumor therapy owing to the rapid development of nanotechnology. In this review, we focus on the applications of Enz-Cats based on ROS in antitumor therapy. Firstly, the definition and category of ROS are introduced, and the key factors enhancing ROS levels are carefully elucidated. Then, the rationally engineered Enz-Cats via different synthetic approaches with high ROS-producing efficiencies are comprehensively discussed. Subsequently, oncotherapy application of Enz-Cats is comprehensively discussed, which integrates diverse synergistic treatment modalities and exhibits high efficiency in ROS generation. Finally, the challenges and future research direction of this field are presented. This review is dedicated to unraveling the enigmas surrounding the interplay of nanomedicine and organisms.

Regional differences of Mycobacterium tuberculosis complex infection and multidrug resistance epidemic in Luoyang.

BACKGROUND: Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. METHODS: From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. RESULTS: Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p < 0.001). Male, re-treated and smear-positive groups were high-burden carriers of MTBC. Individuals aged > 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged < 61 years in the county and township areas. The detection of multidrug-resistant TB (MDR-TB) was higher in the main urban area than in the county and township areas (13.9% vs. 7.8%, p < 0.001). In all areas, MDR-TB groups were dominated by males, patients with a history of TB treatment, and patients aged < 61 years. Stratified analysis of MDR-TB epidemiology showed that MDR4 (INH þ RIF þ EMB þ SM) was predominant in the main urban area, while MDR3 (INH þ RIF þ SM) was predominant in the county and township areas. MDR-TB detection rate and epidemiology differed among the county and township areas. CONCLUSIONS: For local TB control, it is necessary to plan more appropriate and accurate prevention and control strategies according to the regional distribution of MTBC infection.

Examination of learning ability development through the implementation of the "autonomy-collaboration" learning mode grounded in evidence-based medicine practice.

OBJECTIVE: Currently, there are still some shortcomings in EBM education in China.The study aimed to investigate the effectiveness of the novel evidence-based medicine (EBM) learning model of "autonomy-collaboration." METHODS: A total of 91 undergraduate students majoring in clinical medicine at Zhongshan Clinical College of Dalian University from the 2019 batch were selected as the participants in this study. They were instructed to follow the EBM learning model of "autonomy-collaboration." Upon completion of the course, questionnaires, records of participants' sentiments and insights, and evidence-based clinical practice reports were used as indicators to evaluate the effectiveness of the training. RESULTS: This learning modality effectively enhanced independent learning ability of the students, stimulated their interest in learning, and strengthened the communication between students and teachers, thereby improving the quality of teaching. CONCLUSION: The novel EBM learning model of "autonomy-collaboration," exhibited robust effectiveness in instruction and facilitated the seamless integration of theoretical knowledge with clinical practice. Consequently, its widespread adoption is strongly recommended.