A combined solid-state 1H, 13C, 17O NMR and periodic DFT study of hyperfine coupling tensors in paramagnetic copper(II) compounds.

We report solid-state 1H, 13C, and 17O NMR determination of hyperfine coupling tensors (A-tensors) in several paramagnetic Cu(II) (d9, S = 1/2) complexes: trans-Cu(DL-Ala)2·H217O, Cu([1-13C]acetate)2·H2O, Cu([2-13C]acetate)2·H2O, and Cu(acetate)2·H217O. Using these new experimental results and some A-tensor data available in the literature for trans-Cu(L-Ala)2 and K2CuCl4·2H2O, we were able to examine the accuracy of A-tensor computation from a periodic DFT method implemented in the BAND program. We evaluated A-tensors on 1H (I = 1/2), 13C (I = 1/2), 14N (I = 1), 17O (I = 5/2), 39K (I = 3/2), 35Cl (I = 3/2), and 63Cu (I = 3/2) nuclei over a range spanning more than 3 orders of magnitude. We found that the BAND code can reproduce reasonably well the experimental results for both A-tensors and nuclear quadrupole coupling tensors.

Deciphering the role of cuproptosis-related lncRNAs in shaping the lung cancer immune microenvironment: A comprehensive prognostic model.

Cuproptosis plays an important role in cancer, but its role in lung cancer remains unknown. Transcriptional profiles, clinical details and mutation data were acquired from the Cancer Genome Atlas database through a variety of methods. The analysis of this publicly available data was comprehensively performed using R software along with its relevant packages, ensuring a thorough examination of the information. In this study, we conducted a detailed analysis of cuproptosis-related genes and lncRNA co-expression, identifying 129 relevant lncRNAs and establishing a prognostic model with four key lncRNAs (LINC00996, RPARP-AS1, SND1-IT1, TMPO-AS1). Utilizing data from TCGA and GEO databases, the model effectively categorized patients into high- and low-risk groups, showing significant survival differences. Correlation analysis highlighted specific relationships between individual lncRNAs and cuproptosis genes. Our survival analysis indicated a higher survival rate in the low-risk group across various cohorts. Additionally, the model's predictive accuracy was confirmed through independent prognostic analysis and ROC curve evaluations. Functional enrichment analysis revealed distinct biological pathways and immune functions between risk groups. Tumour mutation load analysis differentiated high- and low-risk groups by their mutation profiles. Drug sensitivity analysis and immune infiltration studies using the CIBERSORT algorithm further elucidated the potential treatment responses in different risk groups. This comprehensive evaluation underscores the significance of lncRNAs in cuproptosis and their potential as biomarkers for lung cancer prognosis and immune microenvironment.

Sodium alginate/chitosan-based intelligent multifunctional bilayer film for shrimp freshness retention and monitoring.

Developing bifunctional innovative food packaging for maintaining and monitoring food freshness is crucial for food safety. Here, we prepared tannic acid cinnamaldehyde nanoemulsions through self-assembly and ionic cross-linking between the natural emulsifiers tannic acid and cinnamaldehyde, and were incorporated into chitosan as a protective outer layer. Sodium alginate anchored with alizarin was employed as the sensing inner layer. A pH-sensitive bilayer film integrating real-time monitoring and maintenance of food fresh food freshness was designed using layer-by-layer assembly (LBL) technology. The prepared bilayer film exhibited 100 % UV protection, >99 % antimicrobial effect, and 94.86 % and 97.91 % clearance rates for DPPH and ABTS free radicals, respectively. In addition, the bilayer film exhibited high biosafety and sensitive, reversible, and rapid response to pH/NH3. Shrimp preservation experiments showed that the smart bilayer film could effectively slow down the growth of microorganisms on the surface of shrimp, extend the freshness period of shrimp, and could monitor the freshness of shrimp in real-time through color changes. In conclusion, the prepared SL-CCT bilayer film has excellent potential for food preservation and freshness monitoring, providing a new perspective for design and development of multifunctional smart food packaging films.

Regulating Spin Polarization via Axial Nitrogen Traction at Fe-N5 Sites Enhanced Electrocatalytic CO2 Reduction for Zn-CO2 Batteries.

Single Fe sites have been explored as promising catalysts for the CO2 reduction reaction to value-added CO. Herein, we introduce a novel molten salt synthesis strategy for developing axial nitrogen-coordinated Fe-N5 sites on ultrathin defect-rich carbon nanosheets, aiming to modulate the reaction pathway precisely. This distinctive architecture weakens the spin polarization at the Fe sites, promoting a dynamic equilibrium of activated intermediates and facilitating the balance between *COOH formation and *CO desorption at the active Fe site. Notably, the synthesized FeN5, supported on defect-rich in nitrogen-doped carbon (FeN5@DNC), exhibits superior performance in CO2RR, achieving a Faraday efficiency of 99% for CO production (-0.4 V vs. RHE) in an H-cell, and maintaining a Faraday efficiency of 98% at a current density of 270 mA cm-2 (-1.0 V vs. RHE) in the flow cell. Furthermore, the FeN5@DNC catalyst is assembled as a reversible Zn-CO2 battery with a cycle durability of 24 hours. In-situ IR spectroscopy and density functional theory (DFT) calculations reveal that the axial N coordination traction induces a transformation in the crystal field and local symmetry, therefore weakening the spin polarization of the central Fe atom and lowering the energy barrier for *CO desorption.

Stable and Tunable Quantum Conductance in Spider-Silk-like Synaptic Device for Neurocomputing.

The quantum conductance (QC) behaviors in synaptic devices with stable and tunable conductance states are essential for high-density storage and brain-like neurocomputing (NC). In this work, inspired by the discontinuous transport of fluid in spider silk, a synaptic device composed of a silicon oxide nanowire network embedded with silicon quantum dots (Si-QDs@SiOx) is designed. The tunable QC behaviors are achieved in both the SET and RESET processes, and the QC states exhibit stable retention time exceeding 104 s in the synaptic device and show stable reproducibility after an interval of two months. The synaptic plasticity, including long-term potentiation/depression and Pavlovian conditioning function, is simulated based on the tunable conductance. The mechanism of stable and tunable QC behaviors is analyzed and clarified by beading effect of spider silk in Si-QDs@SiOx nanowires structure. The digit recognition capability of the device is evaluated by simulation using an artificial neural network consisting of the Si-QDs@SiOx-based synaptic device. These results provide insights into the development of neurocomputing systems with high classification accuracy.

Redesigned Electrodes for Improved Intraoperative Nerve Conduction Studies during the Treatment of Peripheral Nerve Injuries.

Traumatic peripheral nerve injuries (PNI), present with symptoms ranging from pain to loss of motor and sensory function. Difficulties in intraoperative visual assessment of nerve functional status necessitate intraoperative nerve conduction studies (INCSs) by neurosurgeons and neurologists to determine the presence of functioning axons in the zone of a PNI. This process, also referred to as nerve "inching", uses a set of stimulating and recording electrode hooks to lift the injured nerve from the surrounding surgical field and to determine whether an electrical stimulus can travel through the zone of injury. However, confounding electrical signal artifacts can arise from the current workflow and electrode design, particularly from the mandatory lifting of the nerve, complicating the definitive assessment of nerve function and neurosurgical treatment decision-making. The objective of this study is to describe the design process and verification testing of our group's newly designed stimulating and recording electrodes that do not require the lifting or displacement of the injured nerve during INCSs. Ergonomic in vivo analysis of the device within a porcine model demonstrated successful intraoperative manipulation of the device, while quantitative nerve action potential (NAP) signal analysis with an ex vivo simulated "inching" procedure on healthy non-human primate nerve tissue demonstrated excellent reproducible recorded NAP fidelity and the absence of NAP signal artifacts at all points of recording. Lastly, electrode pullout force testing determined maximum forces of 0.43 N, 1.57 N, and 3.61 N required to remove the device from 2 mm, 5 mm, and 1 cm nerve models, respectively, which are well within established thresholds for nerve safety. These results suggest that these new electrodes can safely and successfully perform accurate PNI assessment without the presence of artifacts, with the potential to improve the INCS standard of care while remaining compatible with currently used neurosurgical technology, infrastructure, and clinical workflows.

Oxidation Control to Augment Interfacial Charge Transport in Te-P3HT Hybrid Materials for High Thermoelectric Performance.

Organic-inorganic hybrid thermoelectric (TE) materials have attracted tremendous interest for harvesting waste heat energy. Due to their mechanical flexibility, inorganic-organic hybrid TE materials are considered to be promising candidates for flexible energy harvesting devices. In this work, enhanced TE properties of Tellurium (Te) nanowires (NWs)- poly (3-hexylthiophene-2, 5-diyl) (P3HT) hybrid materials are reported by improving the charge transport at interfacial layer mediated via controlled oxidation. A power factor of ≈9.8 µW (mK2)-1 is obtained at room temperature for oxidized P3HT-TeNWs hybrid materials, which increases to ≈64.8 µW (mK2)-1 upon control of TeNWs oxidation. This value is sevenfold higher compared to P3HT-TeNWs-based hybrid materials reported in the literature. MD simulation reveals that oxidation-free TeNWs demonstrate better templating for P3HT polymer compared to oxidized TeNWs. The Kang-Snyder model is used to study the charge transport in these hybrid materials. A large σE0 value is obtained which is related to better templating of P3HT on oxygen-free TeNWs. This work provides evidence that oxidation control of TeNWs is critical for better interface-driven charge transport, which enhances the thermoelectric properties of TeNWs-P3HT hybrid materials. This work provides a new avenue to improve the thermoelectric properties of a new class of hybrid thermoelectric materials.

Possibility of using the imaged capillary isoelectric method as a multi-attribute method for bispecific antibodies.

An imaged capillary isoelectric focusing (icIEF)-based method was developed and validated as a multi-attribute method for a bispecific antibody (BsAb). First, as the traditional application of the icIEF method, it serves as an identity assay and purity assay for the BsAb. Second, the method can also be used as an impurity assay for the homodimer monoclonal antibodies generated during BsAb assembly. The homodimer impurity analysis for BsAb is usually done by hydrophobic interaction chromatography methods in the industry. The icIEF method has good sensitivity (down to 4 µg/mL in a limit of quantitation) when UV fluorescence detection is used, which detects the native fluorescence of proteins. This is the first report that an icIEF method has been applied as impurity assay.

A combination of multiple LC-MS approaches for the comprehensive characterization of cysteine-linked ADCs.

Antibody-drug conjugates (ADCs) represent the forefront of the next generation of biopharmaceuticals. An ADC typically comprises an antibody covalently linked to a cytotoxic drug via a linker, resulting in a highly heterogeneous product. This study focuses on the analysis of a custom-made cysteine-linked ADC. Initially, we developed a LC-MS-based characterization workflow using brentuximab vedotin (Adcetris®), encompassing native intact MS, analysis of reduced chains and subunits under denaturing condition, peptide mapping and online strong cation exchange chromatography coupled with UV and mass spectrometry detection (SCX-UV-MS) applied for brentuximab vedotin first time reported. Subsequently, we applied this in-depth characterization workflow to a custom-made cysteine-linked ADC. The measured drug-to-antibody ratio(DAR) of this ADC is 6.9, further analysis shown that there is a small amount of unexpected over-conjugation. Over-conjugation sites were successfully identified using multiple UHPLC-MS based characterization techniques. Also, one competitively cysteine-conjugated impurity was observed in native intact MS results, by combing native intact MS, reduced chains, subunit analysis and peptide mapping results, the impurity conjugation sites were also identified. Since this molecule is at early development stage, this provides important information for conjugation process improvement and link-drug material purification. SCX-UV-MS approach can separate the custom-made cysteine-linked ADC carrying different payloads and reduce the complexity of the spectra. The integrated approach underscores the significance of combining the SCX-UV-MS online coupling technique with other characterization methods to elucidate the heterogeneity of cysteine-linked ADCs.

Universal Strike-Plating Strategy to Suppress Hydrogen Evolution for Improving Zinc Metal Reversibility.

The development of highly reversible zinc (Zn) metal anodes is pivotal for determining the feasibility of rechargeable aqueous Zn batteries. Our research quantitively evalulates how the hydrogen evolution reaction (HER) adversely affects Zn reversibility in batteries and emphasizes the importance of substrate design in modulating HER and its associated side reactions. When the cathodic reaction is dominated by HER, the Zn electrode exhibits low plating/stripping efficiency, characterized by extensive coverage of a passivation layer that encompasses the electrochemical inactive Zn. Therefore, we propose a strike-plating strategy that modifies the pristine substrate by initiating Zn plating at a high current density for a short time. This straightforward and effective approach has been proven to suppress hydrogen evolution and transform the electrodeposition mode into one dominated by Zn reduction. Notably, Zn metal exhibits exceptionally high average reversibility of 98.80% over 200 h on a stainless steel substrate, which was typically precluded in aqueous electrolytes because of their favorable HER capability. Additionally, our strike-plating strategy demonstrates an appliable pathway to achieve high Zn reversibility on Cu substrate, showing an average efficiency of 99.83% over 540 h at a high areal capacity of 10 mAh cm-2 and high-performance Zn full cells with low N/P ratios. This research provides a foundation for future investigations into the underlying mechanisms of HER and strategies to optimize Zn-based battery performance.

SLC25A19 is a novel prognostic biomarker related to immune invasion and ferroptosis in HCC.

SLC25A19 is a mitochondrial thiamine pyrophosphate (TPP) carrier that mediates TPP entry into the mitochondria. SLC25A19 has been recognized to play a crucial role in many metabolic diseases, but its role in cancer has not been clearly reported. Based on clinical data from The Cancer Genome Atlas (TCGA), the following parameters were analyzed among HCC patients: SLC25A19 expression, enrichment analyses, immune infiltration, ferroptosis and prognosis analyses. In vitro, the SLC25A19 high expression was validated by qRT-PCR and Immunohistochemistry. Subsequently, a series of cell function experiments, including CCK8, EdU, clone formation, trans-well and scratch assays, were conducted to illustrate the effect of SLC25A19 on the growth and metastasis of cancer cells. Meanwhile, indicators related to ferroptosis were also detected. SCL25A19 is highly expressed in HCC and predicts a poor prognosis. Elevated SLC25A19 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Our results indicate that SLC25A19 has a generally good prognosis predictive and diagnostic ability. The results of gene enrichment analyses showed that SLC25A19 is significantly correlated with immune infiltration, fatty acid metabolism, and ferroptosis marker genes. In vitro experiments have confirmed that silencing SLC25A19 can significantly inhibit the proliferation and migration ability of cancer cells and induce ferroptosis in HCC. In conclusion, these findings indicate that SLC25A19 is novel prognostic biomarker related to immune invasion and ferroptosis in HCC, and it is an excellent candidate for therapeutic target against HCC.

Structural Phase Transition and Decomposition of XeF2 under High Pressure and Its Formation of Xe-Xe Covalent Bonds.

Noble gases with inert chemical properties have rich bonding modes under high pressure. Interestingly, Xe and Xe form covalent bonds, originating from the theoretical simulation of the pressure-induced decomposition of XeF2, which has yet to be experimentally confirmed. Moreover, the structural phase transition and metallization of XeF2 under high pressure have always been controversial. Therefore, we conducted extensive experiments using a laser-heated diamond anvil cell technique to investigate the above issues of XeF2. We propose that XeF2 undergoes a structural phase transition and decomposition above 84.1 GPa after laser heating, and the decomposed product Xe2F contains Xe-Xe covalent bonds. Neither the pressure nor temperature alone could bring about these changes in XeF2. With our UV-vis absorption experiment, I4/mmm-XeF2 was metalized at 159 GPa. This work confirms the existence of Xe-Xe covalent bonds and provides insights into the controversy surrounding XeF2, enriching the research on noble gas chemistry under high pressure.

Understanding how cells and organisms keep time during development.

A classical question in biology is how different processes are controlled in space and time, with research pointing to different mechanisms as timers. In this collection of Voices, we asked researchers to define their scientific questions related to time-keeping and the approaches they use to answer them.

The Relationship Between Insulin Resistance Indicated by Triglyceride and Glucose Index and Left Ventricular Hypertrophy and Decreased Left Ventricular Diastolic Function with Preserved Ejection Fraction.

Aim: The evidence on the association between insulin resistance (IR) and the prevalence or incidence of cardiac dysfunction has been controversial, and the relationship between pre-diabetic IR and cardiac function is lacking. Large sample studies in the Chinese general population are urgently needed to explore the association between IR and the risk of left ventricular hypertrophy (LVH) and decreased left ventricular diastolic function with preserved ejection fraction (LVDFpEF). Methods: Based on a National Health Check-up database in China, we conducted a multicenter cross-sectional retrospective study in 344,420 individuals. Furthermore, at a single center, we performed two retrospective longitudinal studies encompassing 8270 and 5827 individuals to investigate the association between IR and the development of new-onset LVH and LVDFpEF, respectively. The median follow-up duration exceeded 2.5 years. The triglyceride and glucose (TyG) index, known for its high sensitivity in detecting IR, serves as a reliable alternative marker of IR. The logistic and cox proportional hazard regression models were used to determine the relationships. Results: In the cross-sectional study, IR showed a positive association with the prevalence of LVH and decreased LVDFpEF after adjusting for confounders. In the longitudinal cohort, IR was also correlated with the new onset of LVH and decreased LVDFpEF, with hazard ratios (HR) of 1.986 (95% CI: 1.307, 3.017) and 1.386 (95% CI: 1.167, 1.647) in the fourth quartile of TyG levels compared to the lowest quartile, respectively, after adjusting for confounders. The subgroup analysis in non-hypertensive or non-diabetic people and the sensitivity analysis in the population with homeostasis model assessment of insulin resistance (HOMA-IR) further verified the above-mentioned results. Conclusion: IR was associated with LVH and decreased LVDFpEF. Effective management of IR may prevent or delay the development of adverse LVH and decreased LVDFpEF.

TXNIP knockdown ameliorates hepatic ischemia/reperfusion injury by inhibiting apoptosis and improving mitochondrial dysfunction via HIF-1α.

This study aims to investigate whether thioredoxin-interacting protein (TXNIP) regulates cell viability, cell apoptosis and mitochondrial damage in OGD/R-induced hepatocytes and to explore its underlying mechanism. AML12 cells were cultured under oxygen-glucose deprivation/reperfusion (OGD/R) conditions. TXNIP mRNA was detected using qRT-PCR, and the TXNIP protein was analyzed using western blotting. TXNIP-targeted short hairpin RNA (sh-TXNIP) lentivirus was used to infect the AML12 cells. CCK8 and TUNEL assays were applied to detect cell viability and apoptosis, respectively. DCFH-DA probe was used to determine reactive oxygen species (ROS) release level, and JC-1 probe was used to evaluate mitochondrial membrane potential (MMP). The localization of TXNIP and HIF-1α was observed using immunofluorescence. Our results showed that TXNIP markedly increased in AML12 cells treated with OGD/R. TXNIP knockdown increased cell viability and reduced cell apoptosis under OGD/R treatment. Moreover, MMP significantly increased and ROS release decreased in cells after TXNIP knockdown under OGD/R treatment. Additionally, TXNIP knockdown markedly increased the expression of HIF-1α. HIF-1α exhibited nuclear translocation following OGD/R induction, and TXNIP knockdown further promoted it. Compared with the OGD/R + sh-TXNIP group, HIF-1α agonist ML228 inhibited cell apoptosis and ROS release, and increased MMP. However, HIF-1α inhibitor PX478 had the opposite effect. In summary, TXNIP deletion ameliorated AML12 cell injury caused by OGD/R via promoting HIF-1α expression and nuclear translocation, manifested by inhibiting cell apoptosis and alleviating mitochondrial dysfunction.

Pooled-analysis of tadalafil and tamsulosin for ureteral calculi.

Objective: Urolithiasis is a common urological diseases and affects the daily life of patients. Medical expulsive therapy has become acceptable for many parents. We conducted a meta-analysis to determine the efficacy and safety of tadalafil compared with tamsulosin for treating distal ureteral stones less than 10 mm in length. Methods: Related studies were identified via searches of the PubMed, Embase, and Cochrane Library databases. All the articles that described the use of tadalafil and tamsulosin for treating distal ureteral stones were collected. Results: A total of 14 studies were included in our meta-analysis. Our results revealed that tadalafil enhanced expulsion rate [odds ratio (OR) = 0.68, 95% confidence interval (CI): 0.47 to 0.98, p = 0.04]; reduced expulsion time [mean difference (MD) = 1.22, 95% CI (0.13, 2.30), p = 0.03]; lowered analgesia use [MD = 38.66, 95% CI (7.56, 69.77), p = 0.01] and hospital visits [MD = 0.14, 95% CI (0.06, 0.22), p = 0.0006]. According to our subgroup analysis, either tadalafil 5 mg or 10 mg did not promote expulsion rate and accelerate expulsion time compared with tamsulosin. But patients receiving 5 mg tadalafil decreased analgesia usage [MD = 101.04, 95% CI (67.56, 134.01), p < 0.00001]. Conclusion: Compared with tamsulosin, tadalafil demonstrates a higher expulsion rate and less expulsion time for patients with distal ureteral stones less than 10 mm with a favorable safety profile.

A native SEC-MS workflow and validation for analyzing drug-to-antibody ratio and drug load distribution in cysteine-linked antibody-drug conjugates.

The development and optimization of Antibody-Drug Conjugates (ADCs) hinge on enhanced analytical and bioanalytical characterization, particularly in assessing critical quality attributes (CQAs). The ADC's potency is largely determined by the average number of drugs attached to the monoclonal antibody (mAb), known as the drug-to-antibody ratio (DAR). Furthermore, the drug load distribution (DLD) influences the therapeutic window of the ADC, defining the range of dosages effective in treating diseases without causing toxic effects. Among CQAs, DAR and DLD are vital; their control is essential for ensuring manufacturing consistency and product quality. Typically, hydrophobic interaction chromatography (HIC) or reversed-phase liquid chromatography (RPLC) with UV detector have been used to quantitate DAR and DLD in quality control (QC) environment. Recently, Native size-exclusion chromatography-mass spectrometry (nSEC-MS) proves the potential as a platformable quantitative method for characterizing DAR and DLD across various cysteine-linked ADCs in research or early preclinical development. In this work, we established and assessed a streamlined nSEC-MS workflow with a benchtop LC-MS platform, to quantitatively monitor DAR and DLD of different chemotype and drug load level cysteine-linked ADCs. Moreover, to deploy this workflow in QC environment, complete method validation was conducted in three independent laboratories, adhering to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2(R1) guidelines. The results met the predefined analytical target profile (ATP) and performance criteria, encompassing specificity/selectivity, accuracy, precision, linearity, range, quantification/detection limit, and robustness. Finally, the method validation design offers a reference for other nSEC-MS methods that are potentially used to determine the DAR and DLD on cysteine-linker ADCs. To the best of our knowledge, this study is the first reported systematic validation of the nSEC-MS method for detecting DAR and DLD. The results indicated that the co-validated nSEC-MS workflow is suitable for DAR and DLD routine analysis in ADC quality control, release, and stability testing.

The Value of 3D SPACE MRI in Differentiating between Sequestrated Lumbar Disc Herniation and Tumors: Two Cases and Literature.

Background: Intervertebral disc herniation, defined as the protrusion or extrusion of the disc mass outside the disc space, is common and easy to diagnose on conventional Magnetic Resonance imaging (MRI) or Computed Tomography (CT) scans. However, the sequestrated disc fragments are challenging to detect, and intervertebral disc mass displacement into the dural sac, which can lead to serious neurological problems such as Cauda equina syndrome (CES). The sequestrated disc fragments do not have specific clinical or radiological characteristics that can differentiate an atypical disc mass from a tumor, making the diagnosis difficult preoperatively. Herein, we describe the use of Sampling Perfection with Application Optimized Contrast using different flip angle Evolution in Magnetic Resonance Imaging (3D SPACE MRI) in the diagnosis of the intervertebral disc fragment that mimicked a tumor. Case presentation: In this study, we report two cases of sequestered lumbar disc herniation. The first case was a 37-year-old patient with a 2-year history of intermittent left lower limb pain that aggravates with exercise and is relieved at rest, while the second case was a 42-year-old patient with a history of 40 days of numbness and pain in the left lower limb. Conclusion: 3D SPACE MRI is a beneficial diagnostic imaging tool for discriminating between disc mass that mimics a tumor and a tumor before surgery. If the disc fragment mimicking a tumor can be identified before the operation, open surgical treatment won't be necessary for all patients.

Epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China during 2017-2022.

Background: Wuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic. Objective: This study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017-2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools. Methods: This study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis. Results: From 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools. Conclusion: We successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

The role of spinal neurons targeted by corticospinal neurons in central poststroke neuropathic pain.

BACKGROUND: Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood. METHODS: By lesioning the lateral thalamic nuclei, we first established a CPSP model that exhibits mechanical and thermal hypersensitivity. Innocuous mechanical stimuli following the thalamic lesion evoked robust neural activation in somatosensory corticospinal neurons (CSNs), as well as in the deep dorsal horn, where low threshold mechanosensory afferents terminate. In this study, we used viral-based mapping and intersectional functional manipulations to decipher the role of somatosensory CSNs and their spinal targets in the CPSP pathophysiology. RESULTS: We first mapped the post-synaptic spinal targets of lumbar innervating CSNs using an anterograde trans-synaptic AAV1-based strategy and showed these spinal interneurons were activated by innocuous tactile stimuli post-thalamic lesion. Functionally, tetanus toxin-based chronic inactivation of spinal neurons targeted by CSNs prevented the development of CPSP. Consistently, transient chemogenetic silencing of these neurons alleviated established mechanical pain hypersensitivity and innocuous tactile stimuli evoked aversion linked to the CPSP. In contrast, chemogenetic activation of these neurons was insufficient to induce robust mechanical allodynia typically observed in the CPSP. CONCLUSION: The CSNs and their spinal targets are required but insufficient for the establishment of CPSP hypersensitivity. Our study provided novel insights into the neural mechanisms underlying CPSP and potential therapeutic interventions to treat refractory central neuropathic pain conditions.