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Abstract Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE -/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE -/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.

Abstract Background We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Abstract Fast-charging, non-aqueous lithium-based batteries are desired for practical applications. In this regard, LiMn2O4 is considered an appealing positive electrode active material because of its favourable ionic diffusivity due to the presence of three-dimensional Li-ion diffusion channels. However, LiMn2O4 exhibits inadequate rate capabilities and rapid structural degradation at high currents. To circumvent these issues, here we introduce quintuple low-valence cations to increase the entropy of LiMn2O4. As a result, the entropy-increased LiMn2O4-based material, i.e., LiMn1.9Cu0.02Mg0.02Fe0.02Zn0.02Ni0.02O4, when tested in non-aqueous lithium metal coin cell configuration, enable 1000 cell cycles at 1.48 A g−1 (corresponding to a cell charging time of 4 minutes) and 25°C with a discharge capacity retention of about 80%. We demonstrate that the increased entropy in LiMn2O4 leads to an increase in the disordering of dopant cations and a contracted local structure, where the enlarged LiO4 space and enhanced Mn-O covalency improve the Li-ion transport and stabilize the diffusion channels. We also prove that stress caused by cycling at a high cell state of charge is relieved through elastic deformation via a solid-solution transition, thus avoiding structural degradation upon prolonged cycling.

Abstract Background Tuberculosis (TB) continues to be a major global health burden, and co-infection with other pathogens further complicates the diagnosis and treatment of this infectious disease. The present retrospective study aimed to evaluate the clinical utility of nanopore sequencing in identifying co-infection caused by Mycobacterium tuberculosis (M.tb) and other pathogens. Methods Patients with M.tb co-infection from December 2021 to March 2023 at the Jiangxi Provincial Chest Hospital were retrospectively studied. Data were collected including demographics, symptoms, imaging findings, pathogen diagnosis tests, and treatment history. Pathogen tests involved culture, AFB smear, Xpert MTB/RIF, and nanopore sequencing. Results The enrolled patients included 20 M.tb cases and three nontuberculous mycobacteria (NTM) cases co-infected with other pathogens. Common clinical symptoms included cough (47.83%), expectoration (34.78%), and asthma (17.39%). Radiological examinations showed typical features of pulmonary tuberculosis, including nodules (73.91%), cord-like shadows (34.78%), cavities (34.78%), and destroyed lung manifestations (17.39%). Nanopore sequencing identified M.tb in a significant majority of the cases (86.96%), outperforming traditional culture tests (39.13%), acid-fast bacilli (AFB) tests (27.27%), and Xpert MTB/RIF (53.84%) tests. Notably, nanopore sequencing revealed that M.tb was frequently co-infected with Candida albicans, Klebsiella pneumoniae, and Mycobacterium abscessus. Three specific cases of co-infection with distinct diagnosis and treatment characteristics were presented in detail. They illustrated the complexity of TB co-infection management and the potential of nanopore sequencing for accurate diagnosis and informing the tailored therapeutic approaches. Conclusion Nanopore sequencing-based metagenomics method can help clinicians to identify TB co-infection patterns and formulate a rational drug regimen in time.

Background: Altered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders. Objective: To investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study. Methods: We selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders). Results: We observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95 % confidence interval [CI]: 0.774–0.958, P = 0.006, PFDR = 0.078), epilepsy (OR = 0.927, 95 % CI: 0.880–0.976, P = 0.004, PFDR = 0.078), focal epilepsy (OR = 0.928, 95 % CI: 0.874–0.986, P = 0.016, PFDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95 % CI: 0.964–0.999, P = 0.041, PFDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95 % CI: 0.81–0.96, P

Abstract Background About 8% of TB cases worldwide are estimated to have rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), ranging from 5 to 11% regions. However, Hr-TB has not received much attention while comparing to be given high priority to the management of rifampicin-resistant tuberculosis (RR-TB). This study aimed to compare the differences of treatment effects for Hr-TB and RR-TB, so as to intensify the treatment and management of Hr-TB. Methods A retrospective study was used to collect bacteriologically positive retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis, who were conducted at 29 tuberculosis control institutions in China from July 2009 to June 2021. We assessed effectiveness and safety of retreated patients with isoniazid/ rifampicin resistant pulmonary tuberculosis. Results A total of 147 with either positive smear or cultures were enrolled, and 80 cases were in Hr-TB group and 67 cases were in RR-TB group. There was no significant difference in terms of age, sex, body mass, type of retreatment and comorbid diabetes between the two groups (P > 0.05). The rate of number of lesions involving lung fields ≥ 3 in Hr-TB group 75.9% (60/79) was significantly higher than RR-TB group 56.7% (38/67) (χ2 = 6.077, P = 0.014). There was no statistically significant difference (P = 0.166) with regard to the treatment outcomes of the two groups, the cure rates were 54.7% (41/75) and 53.6% (30/56), respectively, and the failure rate in Hr-TB group 22.7% (17/75) was 10% higher than RR-TB group 10.7% (6/56). The rate of negative sputum smear at the end of the second month (65.7%) in the Hr-TB group was significantly lower than that in the RR-TB group (85.7%) (P = 0.025). There were no significant differences in the incidences of serious adverse reactions and chest X-ray changes between the two groups (P > 0.05). During the 5-year follow-up, recurrence in the Hr-TB group (7 cases, 14.9%) was no significantly lower than that in the RR-TB group (4 cases, 11.8%) (P = 0.754). Conclusion The treatment of retreated Hr-TB patients was difficult and could be statistically similar or considerably worse than RR-TB. It’s urgent to conduct further evaluation of the treatment status quo to guide the guideline development and clinical practice of Hr-TB patients.

Abstract Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Herein, a unified protocol for a variety of intermolecular Heck-type functionalizations of C sp2 -H bond of alkenes has been developed by thianthrenation. The reaction features metal-free and operationally simple conditions for exclusive cine-selective C-H functionalization of aliphatic and aryl alkenes to forge C-C, C-N, C-P, and C-S bonds at room temperature, providing a general protocol for intermolecular Heck-type reaction of alkenes with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo cine-sulfonylation, cyanation, amination to afford alkenyl sulfones, alkenyl nitriles and enamines.

Abstract Background Transforming waste and nonfood materials into bulk biofuels and chemicals represents a major stride in creating a sustainable bioindustry to optimize the use of resources while reducing environmental footprint. However, despite these advancements, the production of high-value natural products often continues to depend on the use of first-generation substrates, underscoring the intricate processes and specific requirements of their biosyntheses. This is also true for Streptomyces lividans, a renowned host organism celebrated for its capacity to produce a wide array of natural products, which is attributed to its genetic versatility and potent secondary metabolic activity. Given this context, it becomes imperative to assess and optimize this microorganism for the synthesis of natural products specifically from waste and nonfood substrates. Results We metabolically engineered S. lividans to heterologously produce the ribosomally synthesized and posttranslationally modified peptide bottromycin, as well as the polyketide pamamycin. The modified strains successfully produced these compounds using waste and nonfood model substrates such as protocatechuate (derived from lignin), 4-hydroxybenzoate (sourced from plastic waste), and mannitol (from seaweed). Comprehensive transcriptomic and metabolomic analyses offered insights into how these substrates influenced the cellular metabolism of S. lividans. In terms of production efficiency, S. lividans showed remarkable tolerance, especially in a fed-batch process using a mineral medium containing the toxic aromatic 4-hydroxybenzoate, which led to enhanced and highly selective bottromycin production. Additionally, the strain generated a unique spectrum of pamamycins when cultured in mannitol-rich seaweed extract with no additional nutrients. Conclusion Our study showcases the successful production of high-value natural products based on the use of varied waste and nonfood raw materials, circumventing the reliance on costly, food-competing resources. S. lividans exhibited remarkable adaptability and resilience when grown on these diverse substrates. When cultured on aromatic compounds, it displayed a distinct array of intracellular CoA esters, presenting promising avenues for polyketide production. Future research could be focused on enhancing S. lividans substrate utilization pathways to process the intricate mixtures commonly found in waste and nonfood sources more efficiently.

ABSTRACTStaphylococcus aureus, a representative gram-positive bacterium, is a common infectious pathogen widely present in the natural environment. The increasing application of antibiotics is witnessing an increment in the number of clinically resistant strains (such as methicillin-resistant S. aureus [MRSA]), which has posed a great challenge to antimicrobial therapy. In this study, a novel MRSA phage, SauPS-28, was isolated from the lake water of the Guangxi Zhuang Autonomous Region. This phage has an incubation period of approximately 30 min, a lysis period of approximately 40 min, and a burst size of approximately 25 PFU/cell. The isolated phage exhibited good biological stability at a pH range of 6.0–9.0 and temperature range of 4°C–37°C. In addition, the identification of an elongated tail using transmission electron microscopy confirmed that SauPS-28 belongs to the long-tailed phage family. Whole-genome sequencing analysis revealed that SauPS-28 has a 43,286-bp-long genome with 31.03% G + C content. Moreover, SauPS-28 exhibited 95.69% sequence identity with ECel-2020k, while the query coverage was only 66%, which is a newly discovered phage. Whole-genome functional annotation results revealed that SauPS-28 had 68 open reading frames (ORFs). Of these, 30 ORFs are unknown proteins. The results suggest that SauPS-28 could be a lysogenic phage strain. This study thus provides preliminary data to conduct further in-depth analysis of the mechanism of phage–host interaction and provides a reference value for phage therapy.IMPORTANCEIn recent years, drug-resistant bacterial infections have become increasingly serious. As a kind of virus with the ability to infect and lyse drug-resistant bacteria, phage is expected to be a new therapeutic method. In this study, we isolated and purified a new methicillin-resistant Staphylococcus aureus bacteriophage SauPS-28, studied a series of biological characteristics of the bacteriophage, analyzed the genome and structural proteome data of the bacteriophage, and provided reference data for further study of the interaction mechanism between bacteriophage and host bacteria and promoted new antibacterial strategies.

Abstract Background Oxytetracycline which is derived from Streptomyces rimosus, inhibits a wide range of bacteria and is industrially important. The underlying biosynthetic processes are complex and hinder rational engineering, so industrial manufacturing currently relies on classical mutants for production. While the biochemistry underlying oxytetracycline synthesis is known to involve polyketide synthase, hyperproducing strains of S. rimosus have not been extensively studied, limiting our knowledge on fundamental mechanisms that drive production. Results In this study, a multiomics analysis of S. rimosus is performed and wild-type and hyperproducing strains are compared. Insights into the metabolic and regulatory networks driving oxytetracycline formation were obtained. The overproducer exhibited increased acetyl-CoA and malonyl CoA supply, upregulated oxytetracycline biosynthesis, reduced competing byproduct formation, and streamlined morphology. These features were used to synthesize bhimamycin, an antibiotic, and a novel microbial chassis strain was created. A cluster deletion derivative showed enhanced bhimamycin production. Conclusions This study suggests that the precursor supply should be globally increased to further increase the expression of the oxytetracycline cluster while maintaining the natural cluster sequence. The mutagenized hyperproducer S. rimosus HP126 exhibited numerous mutations, including large genomic rearrangements, due to natural genetic instability, and single nucleotide changes. More complex mutations were found than those typically observed in mutagenized bacteria, impacting gene expression, and complicating rational engineering. Overall, the approach revealed key traits influencing oxytetracycline production in S. rimosus, suggesting that similar studies for other antibiotics could uncover general mechanisms to improve production.

Abstract Six-membered N-containing heterocycles, such as 2-piperidinone derivatives, with diverse substitution patterns are widespread in natural products, drug molecules and serve as key precursors for piperidines. Thus, the development of stereoselective synthesis of multi-substituted 2-piperidinones are attractive. However, existing methods heavily rely on modification of pre-synthesized backbones which require tedious multi-step procedure and suffer from limited substitution patterns. Herein, an organophotocatalysed [1 + 2 + 3] strategy was developed to enable the one-step access to diverse substituted 2-piperidinones from easily available inorganic ammonium salts, alkenes, and unsaturated carbonyl compounds. This mild protocol exhibits exclusive chemoselectivity over two alkenes, tolerating both terminal and internal alkenes with a wide range of functional groups.

Background: In this study, we utilized whole genome sequencing (WGS) of clinical extremely drug-resistant tuberculosis (EDR-TB) strains collected during 2014–2020 in Beijing to detect clustered strains. Methods: A retrospective cohort study was conducted by inclusion of EDR-TB patients with positive cultures in Beijing between 2014 and 2020. Results: A total of 95 EDR-TB patients were included in our analysis. Up on the WGS based genotyping, 94 (94/95, 98.9%) out of 95 were identified as lineage 2 (East Asia). The pairwise genomic distance analysis identified 7 clusters, ranging in size from 2 to 5 isolates. The clustering rate of EDR-TB was 21.1%; while no patients had significantly higher odds of clustering. All isolates harbor rpoB RRDR mutations that confer RIF resistance and katG or inhA promoter mutations that confer INH resistance. Of 95 EDR-TB isolates, a total of 15 mutation types were recorded in the transcriptional regulator mmpR5. In vitro susceptibility testing results revealed that 14 (14/15, 93.3%) out of 15 mutation types were resistant to CFZ; whereas only 3 (3/15, 20.0%) showed resistance to BDQ. Interestingly, 12 isolates harbored mutations within rrl locus, whereas only mutations at positions 2294 and 2296 conferred CLA resistance. Favorable outcomes of EDR-TB patients were positively associated with more effective drugs in the regimes. Conclusion: WGS data demonstrate limited transmission of EDR-TB in this metropolis city. WGS-based drug susceptibility predictions will bring benefits to EDR-TB patients to formulate optimal therapeutic regimens.

Abstract Objective The cortical representation of emotions is complex, and cortical mapping of emotional experience is incomplete. We aimed to contribute to cortical mapping of emotional experience. Methods Clinical data from 400 patients with medically refractory epilepsy who underwent stereo‐electroencephalography implantation for localization of the epileptogenic zone at the Beijing Institute of Functional Neurosurgery between October 2015 and June 2021 were collected retrospectively. Furthermore, we reviewed studies that described cortical mapping of emotional experience through electrical cortical stimulation (ECS). Affective responses similar to ictal aura and electrode contacts located in the SOZ were excluded to investigate emotional experiences in normal brain regions. Results Emotional experiences were evoked by stimulation at 10 electrode contacts in the seven patients, including five contacts that evoked mirth and excitement, one contact that evoked calmness, three contacts that evoked fear, and one contact that evoked sadness. In addition, 21 studies that evaluated emotional experiences in response to cortical electrical stimulation were reviewed. Emotions were distributed in the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex. Significance We provided additional evidence that brain regions including the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex were associated with emotional experience.

Abstract α-Tertiary aliphatic amides are key elements in organic molecules, which are abundantly present in natural products, pharmaceuticals, agrochemicals, and functional organic materials. Enantioconvergent alkyl-alkyl bond-forming process is one of the most straightforward and efficient, yet highly challenging ways to build such stereogenic carbon centers. Herein, we report an enantioselective alkyl-alkyl cross-coupling between two different alkyl electrophiles to access α-tertiary aliphatic amides. With a newly-developed chiral tridentate ligand, two distinct alkyl halides were successfully cross-coupled together to forge an alkyl-alkyl bond enantioselectively under reductive conditions. Mechanistic investigations reveal that one alkyl halides exclusively undergo oxidative addition with nickel versus in-situ formation of alkyl zinc reagents from the other alkyl halides, rendering formal reductive alkyl-alkyl cross-coupling from easily available alkyl electrophiles without preformation of organometallic reagents.

One-dimensional (1D) van der Waals (vdW) materials have garnered significant attention for their unique structures and properties, making them promising candidates for various applications in optoelectronics, catalysis, energy storage, and sensors. However, further advancements are required to fully exploit their potential as energy storage devices. This study presents an anode design paradigm utilizing 1D vdW-based V2PS10 crystals characterized by large vdW gaps, a small bandgap, and distinctive chemical compositions that favor lithium storage. To enhance their performance, we employ surface modification techniques to create V2PS10 @C composites, where conductive carbon is integrated with V2PS10 crystals. This modification significantly improves electron transport and Li-ion diffusion within the composite anodes. The resulting composite anodes exhibit exceptional electrochemical properties, including a high discharge capacity of 1154 mAh g−1 after the 50th cycle at 0.1 A g−1, superior rate performance with a current density of 561 mAh g−1 at 10 A g−1, and prolonged cycling stability, maintaining a capacity of 605 mAh g−1 for up to 800 cycles at 5 A g−1. These remarkable electrochemical performances underscore the immense potential of 1D vdW-based materials as next-generation anodes for lithium-ion batteries.

BackgroundIn the fight against tuberculosis, besides chemotherapy, the regulation of oxidative stress (OS) has also aroused people’s interest in host-oriented therapy. However, there is limited research on the genes involved in reactive oxygen species (ROS) production and clearance in macrophages infected with Mycobacterium tuberculosis (MTB). This study analyzes and explores this to provide a basis for exploring new targets for antituberculosis treatments.MethodsWe established a macrophage model infected with MTB, counted intracellular bacteria, and determined the ROS produced using flow cytometry. We conducted ribonucleic acid sequencing, screened differentially expressed genes through transcriptomic methods, and validated the expression of them through reverse transcription-quantitative polymerase chain reaction.ResultsThe ROS of macrophages increased with intracellular bacteria at 4 h after infection with MTB and reached its peak at 48 h, surpassing the uninfected macrophages (p < 0.05). A total of 1,613 differentially expressed genes were identified after infection with MTB, of which 458 were associated with ROS, with over 50% involved in the response of organelles and biological processes to stimuli. We analyzed and identified six genes. After macrophage infection with MTB, the expression of CAMK2B increased, whereas the expression of CYBB decreased (p < 0.05). The expression of GPX3 and SOD2 increased, whereas the expression of CAT decreased (p < 0.05).ConclusionThe ROS-related differentially expressed genes between MTB infected and uninfected macrophages may be related to some organelles and involved in various biological processes, molecular functions, and signaling pathways. Among them, CAMK2B, GPX3, and SOD2 may be related to ROS.

Objective: Solve the problems of poor positioning accuracy and low efficiency of end effectors in the sorting process of parallel food sorting robots. Methods: An intelligent control of the end-effector of a parallel food sorting robot combining fuzzy system, fuzzy neural network and inverse control algorithm was proposed. The modeling information was approximated by the fuzzy system, the unmodeled information was approximated and predicted by the fuzzy neural network, and the inversion control completed the control output. Finally, the experimental verification is carried out. Results: Compared with the traditional control method, the proposed control method had good tracking accuracy and control efficiency of the end effector, the error of the end effector was less than 0.3 mm, and the sorting efficiency reached 1.99 s-1. Conclusion: This control method can achieve accurate, efficient and stable position tracking.

Stable boundary layer height (SBLH) is an important parameter to characterize the characteristics and vertical structure of the nocturnal lower atmosphere at night. The distribution of SBLH has obvious spatial and temporal differences, and there are many meteorological factors affecting the SBLH, but at present, there are few quantitative studies on the effects of near-surface meteorological factors on the SBLH in the desert hinterland. This study was based on GPS sounding balloon data, near-surface meteorological observation data, and ERA5 data from Tazhong Station (TZ) in the Taklamakan Desert (TD) collected in July 2017, 2019, and 2021. The variation characteristics of the SBLH and its relationship with near-surface meteorological factors are described. We quantitatively analyzed the degree of influence of near-surface meteorological factors affecting the SBLH and verified it using a model. The study also elucidates the possible formation mechanism of the SBLH in the TD hinterland. The SBLH in the TD hinterland trended upward in July 2017, 2019, and 2021, which is consistent with the changes in meteorological factors, according to the near-surface meteorological observation and ERA5 data. Therefore, we think that an inherent connection exists between near-surface meteorological factors and the SBLH. The results of correlation analysis show that complex internal connections and interactions exist among the meteorological factors near the ground; some thermal, dynamic, and other meteorological factors strongly correlate with the SBLH. Having established the change in SBLH (ΔSBLH) and in major thermal, dynamic, and other meteorological factors (Δ), the linear regression equation between them revealed that near-surface meteorological factors can affect the SBLH. The dynamic factors have a stronger influence on the ΔSBLH than thermal and other factors. The results of model validation based on the variable importance projection (VIP) also confirmed that the SBLH in the TD hinterland is jointly affected by dynamic and thermal factors, but the dynamic factors have a stronger impact. The mechanism through which the SBLH forms is relatively complex. At night, surface radiative cooling promotes the formation of a surface inversion layer, and low-level jets strengthen wind shear, reducing atmospheric stability. The combined effects of heat and dynamics play an important role in dynamically shaping the SBLH. This study helps us with accurately predicting and understanding the characteristics of the changes in and the factors influencing the SBLH in the TD hinterland, providing a reference for understanding the mechanism through which the SBLH forms in this area. At the same time, it provides a scientific basis for regional weather and climate simulation, meteorological disaster defense, air quality forecasting, and model parameterization improvement.

ZBLAN fiber is widely used in the mid-infrared band, mainly for spectrum, sensing, laser power transmission, fiber laser, and amplifier. By tapering the soft glass optical fiber such as ZBLAN fiber to microfiber, the waveguide behavior can be tailored in the mid-IR spectral range to realize large normal waveguide dispersion. However, the tunability of the dispersion and nonlinearity must be further explored. Because hollow waveguides offer various compelling features, we proposed and designed a hollow ZBLAN microfiber to adjust the dispersion and nonlinearity and numerically investigated the fundamental propagation characteristics of hollow ZBLAN microfibers within the 2– $5~\mu $ m mid-infrared spectral range. The three-layer-dielectric circular waveguide structure was modeled, and the waveguide dispersion, group velocity dispersion, and nonlinearity coefficients of hollow ZBLAN microfibers were investigated. The numerical results showed that the hollow ZBLAN microfiber exhibits broadband dispersion compensation and tunable nonlinear coefficient when its geometry is tailored. The proposed method can be used to manipulate the propagation characteristics of the microfiber in the mid-infrared regime, and the results provide a reference for the design of high-performance mid-infrared optoelectronic devices.

Abstract Objectives We investigated both the metabolic differences and interictal/ictal discharges of the anterior nucleus of the thalamus (ANT) in patients with epilepsy to clarify the relationship between the ANT and the epileptic network. Methods Nineteen patients with drug‐resistant epilepsy who underwent stereoelectroencephalography were studied. Metabolic differences in ANT were analyzed using [18F] fluorodeoxyglucose–positron emission tomography with three‐dimensional (3D) visual and quantitative analyses. Interictal and ictal discharges in the ANT were analyzed using visual and time‐frequency analyses. The relationship between interictal discharge and metabolic differences was analyzed. Results We found that patients with temporal lobe epilepsy (TLE) showed significant metabolic differences in bilateral ANT compared with extratemporal lobe epilepsy in 3D visual and quantitative analyses. Four types of interictal activities were recorded from the ANT: spike, high‐frequency oscillation (HFO), slow‐wave, and α‐rhythmic activity. Spike and HFO waveforms were recorded mainly in patients with TLE. Two spike patterns were recorded: synchronous and independent. In 83.3% of patients, ANT was involved during seizures. Three seizure onset types of ANT were recorded: low‐voltage fast activity, rhythmic spikes, and theta band discharge. The time interval of seizure onset between the seizure onset zone and ANT showed two patterns: immediate and delayed. Interpretation ANT can receive either interictal discharges or ictal discharges which propagate from the epileptogenic zones. Independent epileptic discharges can also be recorded from the ANT in some patients. Metabolic anomalies and epileptic discharges in the ANT indicate that the ANT plays a role in the epileptic network in most patients with epilepsy, especially TLE.

Abstract Latexin (LXN) plays an important role in tumorigenesis and inflammatory response and as a tumor suppressor in many tumors. However, whether LXN regulates tumorigenesis through immune regulation remains uncertain. Here, we demonstrate that LXN deficiency increases hematopoietic stem cells, as well as affects the proportion of immune cells in the peripheral system. Animal studies show that mice loss of LXN promotes tumor growth in subcutaneous tumor model and AOM/DSS-induced colorectal cancer model. We found that loss of LXN promotes macrophage M2 polarization and PD-L2 expression in macrophage, thus, inhibits the function of T cells. Adoptive transfer of wild-type macrophage rescues the function of T cells in LXN-deficient mice. LXN deficiency in hematopoietic lineage exacerbates colorectal carcinogenesis, and targeted inhibition of PD-L2 ameliorates cancer growth in LXN-deficient mice. Mechanistically, we demonstrate that LXN inhibits STAT3 transcriptional activity by targeting inhibition of JAK1 in macrophages. LXN deficiency enhances PD-L2 expression rather than PD-L1 in macrophages, which lead to inhibition of T cells in tumor microenvironment. Collectively, we define a critical role of LXN/JAK1/STAT3 signal in macrophage and highlights the potential role of LXN in tumor immune-escape by regulating macrophage polarization, as well as the expression of immune checkpoint PD-L2.

ObjectiveBy studying the surgical outcome of deep brain stimulation (DBS) of different target nuclei for patients with refractory epilepsy, we aimed to explore a clinically feasible target nucleus selection strategy.MethodsWe selected patients with refractory epilepsy who were not eligible for resective surgery. For each patient, we performed DBS on a thalamic nucleus [anterior nucleus of the thalamus (ANT), subthalamic nucleus (STN), centromedian nucleus (CMN), or pulvinar nucleus (PN)] selected based on the location of the patient's epileptogenic zone (EZ) and the possible epileptic network involved. We monitored the clinical outcomes for at least 12 months and analyzed the clinical characteristics and seizure frequency changes to assess the postoperative efficacy of DBS on the different target nuclei.ResultsOut of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and four (8.9%) of them reported being seizure-free for at least 1 year. Among the patients with temporal lobe epilepsy (TLE, n = 36) and extratemporal lobe epilepsy (ETLE, n = 9), 22 (61.1%) and 7 (77.8%) responded to the treatment, respectively. Among the 45 patients who underwent ANT-DBS, 28 (62%) had focal to bilateral tonic-clonic seizures (FBTCS). Of these 28 patients, 18 (64%) responded to the treatment. Out of the 65 included patients, 16 had EZ related to the sensorimotor cortex and underwent STN-DBS. Among them, 13 (81.3%) responded to the treatment, and two (12.5%) were seizure-free for at least 6 months. Three patients had Lennox–Gastaut syndrome (LGS)-like epilepsy and underwent CMN-DBS; all of them responded to the treatment (seizure frequency reductions: 51.6%, 79.6%, and 79.5%). Finally, one patient with bilateral occipital lobe epilepsy underwent PN-DBS, reducing the seizure frequency by 69.7%.SignificanceANT-DBS is effective for patients with TLE or ETLE. In addition, ANT-DBS is effective for patients with FBTCS. STN-DBS might be an optimal treatment for patients with motor seizures, especially when the EZ overlaps the sensorimotor cortex. CMN and PN may be considered modulating targets for patients with LGS-like epilepsy or occipital lobe epilepsy, respectively.

The forward single hadron production process is an important benchmark process for investigating the emergent properties of gluon saturation or the dense gluon system. We present our recent work [1] in which we improve the prediction accuracy of the next-to-leading order calculation of forward single hadron productions in high-p⊥ regions by implementing the threshold resummations in the Color Glass Condensate framework. Our resummed formula provides accurate descriptions of all related data across a range of energies from RHIC to the LHC. This work sheds light on the path for precision study of Color Glass Condensate based on experimental data.

Post-traumatic trigeminal neuropathic pain (PTNP) combined with secondary dystonia are rare sequelae of orofacial injury and often do not respond to conservative treatment. The consensus on treatment for both symptoms is yet to be standardized. This study reports the case of a 57-year-old male patient with left orbital trauma who developed PTNP immediately after the injury and secondary hemifacial dystonia 7 months thereafter. To treat his neuropathic pain, we performed peripheral nerve stimulation (PNS) using a percutaneously implanted electrode to the ipsilateral supraorbital notch along the brow arch, which instantly resolved the patient's pain and dystonia. PTNP was relieved in a satisfactory manner until 18 months after the surgery, despite a gradual recurrence of the dystonia since 6 months after the surgery. To the best of our knowledge, this is the first reported case of PNS used for the treatment of PTNP combined with dystonia. This case report highlights the potential benefits of PNS in relieving neuropathic pain and dystonia and discusses the underlying therapeutic mechanism. Moreover, this study suggests that secondary dystonia occurs due to the uncoordinated integration of afferent sensory and efferent motor information. The findings of the present study indicate that PNS should be considered for patients with PTNP following the failure of conservative treatment. Secondary hemifacial dystonia may benefit from PNS upon further research and long-term assessment.

Abstract Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public. Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins. Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation. Conclusions The present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.

ABSTRACT: Aims: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. Methods: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. Results: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25–34 years (87.50%). Conclusions: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Abstract Obesity is a risk factor for many chronic diseases, and is associated with increased incidence rate of type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. Adipocyte differentiation play critical role during development of obesity. Latexin (LXN), a mammalian carboxypeptidase inhibitor, plays important role in the proliferation and differentiation of stem cells, and highlights as a differentiation-associated gene that was significantly downregulated in prostate stem cells and whose expression increases through differentiation. However, it is unclear whether LXN is involved in adipocyte differentiation. The aim of this study was to evaluate the role of LXN on adipocyte differentiation, as well as its effects on high fat-induced obesity and metabolic disorders. In this study, we determine the expression of LXN in adipose tissue of lean and fat mice by Western blot, qPCR and immunohistochemistry. We found that LXN in fat tissues was continuous increased during the development of diet-induced obesity. We fed wild-type (WT) and LXN−/−mice with high-fat diet (HFD) to study the effects of LXN on obesity and related metabolic functions. We found that mice deficient in LXN showed resistance against high-fat diet (HFD)-induced obesity, glucose tolerance, insulin tolerance and hepatic steatosis. In vitro studies indicated that LXN was highly induced during adipocyte differentiation, and positively regulated adipocyte differentiation and adipogenesis in 3T3-L1 cells and primary preadipocytes. Functional analysis revealed that the expression of LXN was positively regulated by mTOR/RXR/PPARɤ signaling pathway during the differentiation of adipocytes, while LXN deletion decreased the protein level of PPARɤ in adipocyte through enhancing FABP4 mediated ubiquitination, which led to impaired adipocyte differentiation and lipogenesis. Collectively, our data provide evidence that LXN is a key positive regulator of adipocyte differentiation, and therapeutics targeting LXN could be effective in preventing obesity and its associated disorders in clinical settings.

Background. Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods. The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results. Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions. Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Background and objectiveRetreatment pulmonary tuberculosis (PTB) still accounts for a large proportion of tuberculosis, and the treatment outcome is unfavorable. The recurrence of retreatment PTB based on long-term follow-up has not been well demonstrated. This study aimed to evaluate effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis.MethodsThis multicenter cohort study was conducted in 29 hospitals from 23 regions of China from July 1, 2009, to December 31, 2020. Patients were divided into two treatment regimen groups including experimental group [modified regimen (4H-Rt2-E-Z-S(Lfx)/4H-Rt2-E)]and control group [standard regimen (2H-R-E-Z-S/6H-R-E or 3H-R-E-Z/6H-R-E)]. The patients enrolled were followed up of 56 months after successful treatment. We compared the treatment success rate, treatment failure rate, adverse reaction rate, and recurrence rate between two regimens. Multivariate Cox regression model was used to identify the potential risk factors for recurrence after successful treatment with proportional hazards assumptions tested for all variables.ResultsA total of 381 patients with retreatment PTB were enrolled, including 244 (64.0%) in the experimental group and 137 (36.0%) in the control group. Overall, the treatment success rate was significant higher in the experimental group than control group (84.0 vs. 74.5%, P = 0.024); no difference was observed in adverse reactions between the two groups (25.8 vs. 21.2%, P > 0.05). A total of 307 patients completed the 56 months of follow-up, including 205 with the modified regimen and 102 with the standard regimen. Among these, 10 cases (3.3%) relapsed, including 3 in the experimental group and 7 in the control group (1.5% vs 6.9%, P = 0.035). Reduced risks of recurrence were observed in patients treated with the modified regimen compared with the standard regimen, and the adjusted hazard ratio was 0.19 (0.04–0.77).ConclusionThe modified retreatment regimen had more favorable treatment effects, including higher treatment success rate and lower recurrence rate in patients with retreated drug-sensitive PTB.

Background: To adapt the scientific evaluation tool for the confusion evaluation of health rumors and to test this tool to the confusion evaluation of coronavirus disease 2019 (COVID-19)-related health rumors on Chinese online platforms during the outbreak period of COVID-19in China. Methods: The design of our study was systematic evaluation of COVID-19-related health rumors. Retrieved from 7 rumor-repellent platforms, rumors about COVID-19 were collected during the publication from December 1, 2019, to February 6, 2020, and their origins were traced. Researchers evaluated rumors using the confusion evaluation tool in 6 dimensions(creators, evidence selection, evidence evaluation, evidence application, backing and publication platform, conflict of interest). Items were scored using a seven-point Likert scale. The scores were converted into percentages, and the median of rumors from different sources was compared with rank-sum test. Results: Our research included 127 rumors. Scores were converted to percentages, median and interquartile range are used to describe the data. The median score: creators 25.00%(interquartile range, IQR, 16.67-37.50%), evidence selection 27.78% (IQR, 13.89-44.44%),evidence evaluation 33.33% (IQR, 25.00-45.83%), evidence application 36.11% (IQR, 22.22-47.22%), backing and publication platform 8.33% (IQR, 4.17-20.83%), conflict of interest75.00% (IQR, 50.00-83.33%). Almost 40% rumors came from WeChat and the rumors with the lowest scores were concentrated on the WeChat platform. The rumors about prevention methods have relatively lower scores. Conclusion: Most rumors included were not highly confusing for evaluators of this project.WeChat is the "worst-hit area" of COVID-19 related health rumors. More than half rumors focus on the description of prevention methods, which reflects the panic, anxiety and blind conformity of the public under public health emergencies.

Chiral aliphatic amine and alcohol derivatives are difficult to access due to the challenge to differentiate between spatially and electronically similar alkyl groups. Here the authors show a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent enantioselectivity.

Developing drug delivery nanosystems with both anticancer and antibacterial effects is of great clinical value. Herein, we report a facile approach to synthesize Ag and quaternary ammonium salt (QAS) co-decorated mesoporous silica nanoparticles (MSNs), namely, Ag/QAS-MSNs, for synergistic treatment of cancer and bacterial infections. In vitro studies demonstrated that Ag/QAS-MSNs not only had a strong antibacterial activity against the bacterial pathogens but also could efficiently induce cancer cell death through an apoptotic pathway. Moreover, in vivo combination therapy with Ag and QAS in Ag/QAS-MSNs was also tested in a nude mouse tumor model, and a significant synergistic anticancer effect, which is superior to that obtained by therapy with Ag-MSNs or QAS-MSNs alone, was achieved. Such excellent anticancer and antibacterial activity of Ag/QAS-MSNs could be attributed to the synergistic effect of Ag ions and QAS. Thus, Ag/QAS-MSNs have a promising future as potent anticancer agents with high antibacterial performance.

BackgroundSpinal tuberculosis (TB) is one of the most common forms of extrapulmonary tuberculosis, causing increased morbidity and lifelong disabilities. Here, we conducted a retrospective study to determine the impact on patient outcomes of the Xpert MTB/RIF test vs. phenotypical drug susceptibility testing for spinal TB.MethodsIn-patients with spinal TB were enrolled in 2013 and 2017 at Beijing Chest Hospital. Data were collected from an electronic patient record system that documented demographic and clinical characteristics. All the patients were routinely followed-up at 1, 3, 6, 9, and 12 months after surgery during outpatient treatment.ResultsA total of 361 patients affected by spinal TB were enrolled in our analysis, including 178 patients in 2013 and 183 patients in 2017. In 2013, the cumulative postoperative recurrence rate of patients with spinal TB was 23% (41/178), which was significantly higher than that in 2017 (8.2%, 15/183, P < 0.001). Additionally, the patients with spinal TB diagnosed in 2013 relapsed significantly sooner than those in 2017 (P < 0.001). In the multivariate analysis, rifampicin (RIF) resistance was associated with the recurrence of spinal TB. The turnaround time of Xpert ranged from 1 to 3 days, with a median of 1 day (IQR: 1–2). For the phenotypic drug susceptibility test (pDST)-based algorithm, the median turnaround time was 67 days, considerably longer than that of the Xpert-based algorithm (P < 0.001).ConclusionThe RIF resistance is an independent risk factor for postoperative recurrence in patients with spinal TB. Early detection of RIF resistance due to the application of Xpert is an effective strategy to reduce spinal TB recurrence.

The performance of gradient and shim coils affect the quality of magnetic resonance imaging (MRI) directly. Conventional gradient/shim coils have some inherent disadvantages, such as the state of produced magnetic field is single and inflexible, many types of coils are required and the structure is complex, while the matrix gradient coils are able to overcome those problems. This paper introduces the concept and characteristics of matrix gradient coil, and reviews the current progresses in this research topic according to the structure and function of the gradient coil. The development tendency of matrix gradient coil in the future is proposed. In addition, the preliminary research on matrix gradient coil is presented.

Abstract Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

The synthesis of regio- and stereo-defined alkenes with multiple alkyl substituents is an unmet challenge. Here, the authors report a nickel-catalyzed intermolecular cross-dialkylation of alkynes devoid of directing or activating groups to afford multiple aliphatic substituted alkenes in a syn-selective fashion.

Objectives: We described the prevalence of clofazimine (CFZ) resistance in a multidrug-resistant tuberculosis (MDR-TB) cohort in China. We also aimed to identify dynamic changes in CFZ susceptibility and its molecular mechanism after exposure to bedaquiline (BDQ) and/or CFZ. Methods: The experimental settings were conducted based on our MDR-TB cohort receiving BDQ-containing regimens. Sequential isolates were obtained from patients. CFZ and BDQ susceptibility of isolates were determined using the minimum inhibitory concentration (MIC) method. The fragments of Rv0678 and pepQ were sequenced. Results: A total of 277 patients infected with MDR-TB were included in our study. CFZ resistance was noted in 23 (23/277, 8.3%) isolates. The rate of acquired CFZ resistance (12/189, 6.3%) was significantly greater than that of primary resistance (11/88, 12.5%, P = 0.028). Out of 23 CFZ-resistant isolates, five (5/23) were BDQ-resistant, and the other 18 (18/23) were susceptible to BDQ. Of note, nine 9/23) out of 23 CFZ-resistant isolates had mutations within either target genes. Kaplan-Meier analysis demonstrated that the baseline CFZ resistance had no influence on time to culture conversion in our cohort (P = 0.828). Acquired CFZ resistance emerged in eight (8/94, 8.5%) patients during treatment for MDR-TB, including three patients receiving regimens without CFZ. Conclusions: Our results demonstrate the high rate of CFZ resistance among MDR-TB patients in China. Patients treated with BDQ-containing regimens achieve comparative culture conversion rate regardless of baseline CFZ susceptibility. The presence of acquired CFZ-resistance following BDQ treatment without known mutation indicates that other mechanisms conferring cross resistance to these two compounds may exist.

In this paper, the stability analysis problem of time-varying delay systems is studied. Based on recent research on Lyapunov-Krasovskii functionals (LKFs), relaxed conditions have been found to weaken some matrices in terms of LKFs, which means that some integral terms cannot be strictly positive definite. Therefore, motivate by this consideration, a new relaxed condition is constructed to weaken some matrices in constructed LKF. Then, for the sake of obtaining more information of time delays, dynamic delay interval (DDI) method was introduced to address the double integral terms with time-varying delay. Furthermore, some recent technologies are employed to process derivatives of LKF. As a consequence, a less conservative result is obtained. The examples given by previous papers are used to demonstrate the superiority of our work.

Objectives: Based on data for a large population of patients from a single center accumulated over 22 years, the present study aimed to reveal an overall profile of movement disorders (MDs) in terms of their demographic features and surgical treatment. Methods: This study was conducted on 21,005 outpatients (2008–2019) and 5,126 inpatients (1998–2019) with MDs who underwent radiofrequency ablation (RFA) or deep-brain stimulation (DBS). Patients were categorized into those with Parkinson’s disease (PD), essential tremor (ET), dystonia, tics, or involuntary movements (IMs). The clinical data of these patients were analyzed retrospectively. Results: PD accounted for the largest proportion (75.4%) among surgically treated MD patients, and was associated with the highest surgical rate (18.8%), followed by ET (proportion: 12.1%, surgical rate: 10.4%) and dystonia (proportion: 5.7%, surgical rate: 5.7%). The male:female ratio was higher in surgical patients than in outpatients (1.49 vs. 1.27, p