scRNA-Seq: First Atlas and Cellular Landscape of Lacrimal Sac: Implications in Primary Acquired Nasolacrimal Duct Obstruction Pathogenesis.

Purpose: The aim of this study was to describe the transcriptional changes of individual cellular components in the lacrimal sac in patients with primary acquired nasolacrimal duct obstruction (PANDO) and attempt to construct the first lacrimal sac cellular atlas to elucidate the potential mechanisms that may drive the disease pathogenesis. Methods: Lacrimal sac samples were obtained intra-operatively during the endoscopic dacryocystorhinostomy (EnDCR) procedure from five patients. Single-cell RNA sequencing was performed to analyze each individual cell population including epithelial and immune cells during the early inflammatory and late inflammatory phases of the disease. Results: Eleven cell types were identified among 25,791 cells. T cells and B cells were the cell populations with the greatest variation in cell numbers between the two phases and were involved in immune response and epithelium migration-related pathways. The present study showed that epithelial cells highly expressed the genes of senescence-associated secretory phenotype (SASP) and were involved in influencing the inflammation, neutrophil chemotaxis, and migration during the late inflammatory stage. Enhanced activity of CXCLs-CXCRs between the epithelial cells and neutrophils was noted by the cell-cell communication analysis and is suspected to play a role in inflammation by recruiting more neutrophils. Conclusions: The study presents a comprehensive single-cell landscape of the lacrimal sac cells in different phases of PANDO. The contribution of T cells, B cells, and epithelial cells to the inflammatory response, and construction of the intercellular signaling networks between the cells within the lacrimal sac has further enhanced the present understanding of the PANDO pathogenesis.

Primary Lacrimal Sac Tumors with Extension into Vicinity: Outcomes with Endoscopy-Assisted Modified Weber-Ferguson's Approach.

PURPOSE: To evaluate the outcomes of endoscopy-assisted modified Weber-Ferguson's approach in the management of primary lacrimal sac tumors with extension into the neighboring tissues. METHODS: A retrospective interventional study was performed on all patients with lacrimal sac tumors treated with the endoscopy-assisted modified Weber-Ferguson approach between January 2010 and June 2022 at the Shanghai Ninth People's Hospital, China. Data assessed include demographics, clinical presentations, imaging features, surgical techniques, histopathology, adjuvant modalities of management, complications, and outcomes. RESULTS: A total of 13 patients were included in the analysis. Epiphora and palpable mass lesion were the presenting complaint in 84.6% (11/13) of the patients. Nearly half of the patients (46.1%, 6/13) were misdiagnosed as lacrimal duct obstruction. All the lacrimal sac tumors in the present series showed uneven enhancement on T1-weighted MRI imaging. Postoperatively, 84.6% (11/13) patients recovered well with excellent esthetics and were disease-free after a mean follow-up of 58.6 months. Two patients who underwent additional exenteration developed recurrence and succumbed (at 41 and 96 months follow up) while they were on palliative chemoradiation. CONCLUSION: The endoscopic-assisted modified Weber-Fergusson surgical approach is effective in providing better visibility and accessibility to lacrimal sac tumors with extension into neighboring tissue.

Molecular epidemiological characteristics of Mycobacterium leprae in highly endemic areas of China during the COVID-19 epidemic.

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

Evaluation of primary acquired nasolacrimal duct obstruction: Comparison of CT-DCG and dacryoendoscopy in accurately localizing the lacrimal drainage obstructions.

OBJECTIVE: To correlate and evaluate the power and limitations of CT-DCG in determining the level and type of lacrimal duct obstruction in comparison to dacryoendoscopy in patients clinically suspected to be having partial or complete primary acquired nasolacrimal duct obstruction (PANDO). METHODS: A retrospective chart review was performed on 1232 lacrimal drainage systems of 957 patients who suffered from primary acquired nasolacrimal duct obstruction (PANDO) at Shanghai Ninth People's Hospital. Patients were examined with CT-DCG and correlated with dacryoendoscopy and the findings of clinical examination. RESULTS: Of the studied patients, 173 were men and 784 were women with an age range of 18-93 years. Of the 1232 lacrimal pathways, good CT-DCG images could be obtained in 980 cases and dacryoendoscopy in 957 cases. Of these complete obstructions were noted in 81% (794/980), and partial obstructions were identified in 19% (186/980) with CT-DCG. CT-DCG and dacryoendoscopy showed 68.4% agreement for the type of the obstruction and 63% for the level of the obstruction. The majority of the obstructions occurred at the sac-duct junction (62.5%) followed by the upper half of the nasolacrimal duct (27.5%). There was a significant difference in the correlation of the obstruction type with age group and with the duration of symptoms. As the duration of symptoms increased, the proportion of complete lacrimal duct obstructions as shown on CT-DCG images increased and the proportion of incomplete obstruction decreased (p = 0.015). CONCLUSIONS: The junction of lacrimal sac and nasolacrimal duct was the most common obstruction site. Age and the duration of symptoms influenced the type of obstruction noted. The degree and level of agreement between the investigations was moderate. A combination of CT-DCG and Dacryoendoscopy could together identify the location more accurately.

Spatiotemporal pattern of leprosy in southwest China from 2010 to 2020: an ecological study.

BACKGROUND: Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. METHODS: This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. RESULTS: A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: -14.0 to - 10.5; P < 0.001). Results of global spatial autocorrelation showed that leprosy cases presented clustering distribution in the study area. Most likely clusters were identified during the study period and were frequently located at Yunnan or the border areas between Yunnan and Guizhou Provinces. Secondary clusters were always located in the western counties, the border areas between Yunnan and Sichuan Provinces. CONCLUSIONS: Geographic regions characterized by clusters with high rates were considered as leprosy high-risk areas. The findings of this study could be used to design leprosy control measures and provide indications to strengthen the surveillance of high-risk areas. These areas should be prioritized in the allocation of resources.

Enhancing squat movement classification performance with a gated long-short term memory with transformer network model.

Bodyweight squat is one of the basic sports training exercises. Automatic classification of aberrant squat movements can guide safe and effective bodyweight squat exercise in sports training. This study presents a novel gated long-short term memory with transformer network (GLTN) model for the classification of bodyweight squat movements. Twenty-two healthy young male participants were involved in an experimental study, where they were instructed to perform bodyweight squat in nine different movement patterns, including one acceptable movement defined according to the National Strength and Conditioning Association and eight aberrant movements. Data were acquired from four customised inertial measurement units placed at the thorax, waist, right thigh, and right shank, with a sampling frequency of 200 Hz. The results show that compared to state-of-art deep learning models, our model enhances squat movement classification performance with 96.34% accuracy, 96.31% precision, 96.45% recall, and 96.32% F-score. The proposed model provides a feasible wearable solution to monitoring aberrant squat movements that can facilitate performance and injury risk assessment during sports training. However, this model should not serve as a one-size-fits-all solution, and coaches and practitioners should consider individual's specific needs and training goals when using it.

Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.

BACKGROUND: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. METHODS: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. RESULTS: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. CONCLUSION: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Multi-objective design and optimization of squeezed branch pile based on orthogonal test.

In recent years, the emergence of the squeezed branch pile has presented a new avenue for civil engineering, offering a distinctive structure and favorable mechanical characteristics. Squeezed branch piles have strong compressive, uplift, and horizontal load resistance capabilities. Due to the existence of discs, the geometric parameters of squeezed branch piles are abundant but important. This article selects number of discs, disc diameter, disc squeeze angle, and disc spacing as the main influencing factors on the bearing capacity of squeezed branch piles and conducts a qualitative analysis of their mechanical properties. The aim of this article is to analyze the different bearing performances of squeezed branch piles through orthogonal experimental design, simulate test conditions using finite element software ABAQUS, obtain relevant data, and finally determine the weight ranking and optimal combination of influencing factors through range analysis to provide better guidance for engineering practices. Through multi-objective optimization design, six optimization objectives including compressive performance, compressive economic efficiency, uplift performance, uplift economic efficiency, maximum horizontal displacement and maximum bending moment of pile body were analyzed. The analysis methods used included comprehensive balance method, queue scoring method, principal component analysis method, entropy weight method, and analytic hierarchy process. The conclusions obtained are similar, and based on the judgment, the squeezed branch pile with 4 discs, disc diameter of 2.5D, disc squeeze angle of 35°, and disc spacing of 3D is considered as the optimal combination under consideration of all optimization objectives.

Rhein attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through NRF2/SLC7A11/GPX4 pathway.

BACKGROUND: Ischemic stroke, a major cause of death and disability worldwide, results from reduced blood flow to the brain, leading to irreversible neuronal damage. Recent evidence suggests that ferroptosis, a form of regulated cell death, plays a critical role in the pathogenesis of ischemic stroke. Rhein, a natural anthraquinone compound, has demonstrated neuroprotective effects; However, its role in ferroptosis and the underlying mechanisms remain unclear. Here, we investigated the protective effects of Rhein against ischemia/reperfusion (I/R) injury in a rat model of middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells. Rhein treatment dose-dependently ameliorated neurological deficits, reduced infarct volume, and attenuated blood-brain barrier (BBB) disruption in the MCAO model. Furthermore, Rhein suppressed oxidative stress, intracellular ROS generation, and ferroptosis-related protein expression in both in vivo and in vitro models. Mechanistically, Rhein protected against OGD/R-induced HT22 cell injury by regulating the NRF2/SLC7A11/GPX4 signaling pathway. This effect was abolished upon NRF2 inhibition, suggesting that Rhein's neuroprotective action is NRF2-dependent. Molecular docking and microscale thermophoresis analyses further supported the direct interaction between Rhein and the ferroptosis-related protein NRF2. Collectively, our findings reveal that Rhein confers neuroprotection against cerebral I/R injury by inhibiting ferroptosis via the NRF2/SLC7A11/GPX4 axis, providing a potential therapeutic avenue for ischemic stroke. AIMS: To investigate the neuroprotective effects of Rhein, a natural anthraquinone compound, against ischemia/reperfusion (I/R) injury and elucidate the underlying mechanisms involving ferroptosis and the NRF2/SLC7A11/GPX4 pathway. METHODS: A rat model of middle cerebral artery occlusion (MCAO) was employed for in vivo assessments, while oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells were used as an in vitro model. Comprehensive analyses, including neurological score assessment, triphenyl tetrazolium chloride staining, Evans Blue leakage assay, intracellular ROS detection, MTT assay, dual-luciferase reporter assay, oxidative stress and Fe2+ content assessment, immunofluorescence, Western blot, flow cytometry, molecular docking, and microscale thermophoresis, were performed to evaluate the effects of Rhein on I/R injury and ferroptosis. RESULTS: Rhein conferred dose-dependent neuroprotection against cerebral I/R injury, reducing infarct volume and blood-brain barrier (BBB) disruption in the MCAO model. In both in vivo and in vitro models, Rhein suppressed oxidative stress, intracellular ROS generation, and ferroptosis-related protein expression. Furthermore, Rhein protected HT22 cells from OGD/R-induced injury by regulating the NRF2/SLC7A11/GPX4 signaling pathway, with NRF2 inhibition abolishing these therapeutic effects. Molecular docking and microscale thermophoresis analyses supported a direct interaction between Rhein and NRF2, a ferroptosis-related protein. CONCLUSION: Rhein attenuates cerebral I/R injury by inhibiting ferroptosis via the NRF2/SLC7A11/GPX4 axis, highlighting its potential as a therapeutic agent for ischemic stroke.

Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities.

γδ-T cells are innate-like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ-T cells (γδ-T-EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether γδ-T-EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that γδ-T-EVs had immune adjuvant effects on antigen-presenting cells, as revealed by enhanced expression of antigen-presenting and co-stimulatory molecules, secretion of pro-inflammatory cytokines and antigen-presenting ability of DCs after γδ-T-EVs treatment. The γδ-T-EVs-based vaccine was designed by loading tumor-associated antigens (TAAs) into γδ-T-EVs. Compared with γδ-T-EVs, the γδ-T-EVs-based vaccine effectively promoted more tumor-specific T-cell responses. In addition, the vaccine regimen preserved direct antitumor effects and induced tumor cell apoptosis. Interestingly, the allogeneic γδ-T-EVs-based vaccine showed comparable preventive and therapeutic antitumor effects to their autologous counterparts, indicating a better way of centralization and standardization in clinical practice. Furthermore, the allogeneic γδ-T-EVs-based vaccine displayed advantages over the DC-EVs-based vaccine through their dual antitumor activities. This study provides a proof-of-concept for using the allogeneic γδ-T-EVs-based vaccine in cancer control.

Selenium deficiency caused hepatitis in chickens via the miR-138-5p/SelM/ROS/Ca2+ overload pathway induced by hepatocyte necroptosis.

Selenoprotein M (SelM), a key thioredoxin like enzyme in the endoplasmic reticulum (ER), is closely related to hepatocyte degeneration. However, the role of miR-138-5p/SelM and necroptosis in chicken SelM-deficient hepatitis and the specific biological mechanism of liver inflammation caused by SelM deficiency have not been elucidated. We established an in vivo chicken liver Se deficiency model by feeding a low-Se diet. The miR-138-5p knockdown and overexpression models and SelM knockdown models were established in LMH cells for an in vitro study. Transmission electron microscopy, H&E staining, Fluo4-AM/ER staining, and flow cytometry were used to detect the morphological changes in chicken liver tissue and the expression changes of necroptosis and inflammation in chicken liver cells. We observed that Se deficiency resulted in liver inflammation, up-regulation of miR-138-5p expression and down-regulation of SelM expression in chickens. Oxidative stress, Ca2+ overload, energy metabolism disorder and necroptosis occurred in chicken liver tissue. Importantly, ROS and the Ca2+ inhibitor could effectively alleviate the energy metabolism disorder, necroptosis and inflammatory cytokine secretion caused by miR-138-5p overexpression and SelM knockdown in LMH cells. In conclusion, selenium deficiency causes hepatitis by upregulating miR-138-5p targeting SelM. Our research findings enrich our knowledge about the biological functions of SelM and provide a theoretical basis for the lack of SelM leading to liver inflammation in chickens.

Microdosimetric assessment about proton spread-out Bragg peak at different depths based on the normal human mesh-type cell population model.

Objective.In clinical proton therapy, the spread-out Bragg peak (SOBP) is commonly used to fit the target shape. Dose depositions at microscopic sites vary, even with a consistent absorbed dose (D) in SOBP. In the present study, monolayer mesh-type cell population models were developed for microdosimetric assessment at different SOBP depths.Approach.Normal human bronchial epithelial (BEAS-2B) and hepatocytes (L-O2) mesh-type cell models were constructed based on fluorescence tomography images of normal human cells. Particle transport simulation in cell populations was performed coupled with Monte Carlo software PHITS. The relationship between microdosimetry and macrodosimetry of SOBP at different depths was described by analyzing the microdosimetric indicators such as specific energyz,specific energy distributionfz,D,and relative standard deviationσz/z¯within cells. Additionally, the microdosimetric distributions characteristics and their contributing factors were also discussed.Main results.The microscopic dose distribution is strongly influenced by cellular size, shape, and material. The mean specific energyz¯of nucleus and cytoplasm in the cell population is greater than the overall absorbed dose of the cell population model (Dp), with a maximumz¯/Dpof 1.1. The cellular dose distribution is different between the BEAS-2B mesh-type model and its concentric ellipsoid geometry-type model, which difference inz¯is about 10.3% for the nucleus and about 7.5% for the cytoplasm with the SOBP depth of 15 cm. WhenD= 2 Gy, the maximumzof L-O2 nucleus reaches 2.8 Gy andσz/z¯is 5.1% at the mid-depth SOBP (16-18 cm); while the maximumzof the BEAS-2B nucleus reaches 2.2 Gy with only 2.7% ofσz/z¯.Significance.The significant variation of microdosimetric distributions of SOBP different depths indicates the necessity to use mesh-type cell population models, which have the potential to be compared with biological results and build the bio-physical model.

Multiple Mesh-type Real Human Cell Models for Dosimetric Application Coupled with Monte Carlo Simulations.

The mesh-type models are superior to voxel models in cellular dose assessment coupled with Monte Carlo codes. The aim of this study was to expand the micron-scale mesh-type models based on the fluorescence tomography of real human cells, and to investigate the feasibility of these models in the application of various irradiation scenarios and Monte Carlo codes. Six different human cell lines, including pulmonary epithelial BEAS-2B, embryonic kidney 293T, hepatocyte L-02, B-lymphoblastoid HMy2.CIR, Gastric mucosal GES-1, and intestine epithelial FHs74Int, were adopted for single mesh-type models reconstruction and optimization based on laser confocal tomography images. Mesh-type models were transformed into the format of polygon mesh and tetrahedral mesh for the GATE and PHITS Monte Carlo codes, respectively. The effect of model reduction was analyzed by dose assessment and geometry consideration. The cytoplasm and nucleus doses were obtained by designating monoenergetic electrons and protons as external irradiation, and S values with different "target-source" combinations were calculated by assigning radioisotopes as internal exposure. Four kinds of Monte Carlo codes were employed, i.e., GATE with "Livermore," "Standard" and "Standard and Geant4-DNA mixed" models for electrons and protons, as well as PHITS with "EGS" mode for electrons and radioisotopes. Multiple mesh-type real human cellular models can be applied to Monte Carlo codes directly without voxelization when combined with certain necessary surface reduction. Relative deviations between different cell types were observed among various irradiation scenarios. The relative deviation of nucleus S value reaches up to 85.65% between L-02 and GES-1 cells by 3H for the "nucleus-nucleus" combination, while that of 293T and FHs74Int nucleus dose for external beams at a 5.12 cm depth of water is 106.99%. Nucleus with smaller volume is far more affected by physical codes. There is a considerable deviation for dose within BEAS-2B at the nanoscale. The multiple mesh-type real cell models were more versatile than voxel models and mathematical models. The present study provided several models which can easily be extended to other cell types and irradiation scenarios for RBE estimations and biological effect predictions, including radiation biological experiments, radiotherapy and radiation protection.

Multifunctional Redox-Responsive Nanoplatform with Dual Activation of Macrophages and T Cells for Antitumor Immunotherapy.

High expression of programmed death ligand 1 (PD-L1) and strong immune evasion ability of the tumor microenvironment (TME) are maintained through mutual regulation between different immune and stromal cells, which causes obstructions for cancer immunotherapy, especially immunosuppressive M2-like phenotype tumor-associated macrophages (TAMs). Repolarization of TAMs to the M1-like phenotype could secrete proinflammatory cytokines and reverse the immunosuppressive state of the TME. However, we found that reactive oxygen species (ROS) generated by repolarized TAMs could be a double-edged sword: ROS cause a stronger suppressive effect on CD8 T cells through an increased proportion of apoptotic regulatory T (Treg) cells. Thus, simply repolarizing TAMs while ignoring the suppressed function of T cells is insufficient for generating adequate antitumor immunity. Accordingly, we engineered multifunctional redox-responsive nanoplatform NPs (M+C+siPD-L1) with Toll-like receptor agonist (M), catalase (C), and siPD-L1 encased for coregulation of both TAMs and T cells to maximize cancer immunotherapy. Our results demonstrated that NPs (M+C+siPD-L1) showed superior biocompatibility and intratumor accumulation. For in vitro experiments, NPs (M+C+siPD-L1) simultaneously repolarized TAMs to the M1-like phenotype, hydrolyzed extra ROS, knocked down the expression of PD-L1 on tumor cells, and rescued the function of CD8 T cells suppressed by Treg cells. In both orthotopic Hepa1-6 and 4T1 tumor-bearing mouse models, NPs (M+C+siPD-L1) could effectively evoke active systemic antitumor immunity and inhibit tumor growth. The combination of repolarizing TAMs, hydrolyzing extra ROS, and knocking down the expression of PD-L1 proves to be a synergistic approach in cancer immunotherapy.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Skeletal muscle abnormalities, such as muscle mass depletion (sarcopenia) and fatty infiltration of the muscle (myosteatosis), are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt (TIPS). AIM: To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy (HE) and mortality after TIPS. METHODS: The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved. The transversal psoas muscle thickness (TPMT) and psoas muscle attenuation (PMA) measured from the unenhanced abdominal computed tomography (CT) at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis, respectively. The area under curve (AUC) was used to evaluate the discriminative power of TPMT, PMA, and relevant clinical parameters. Fur-thermore, log-rank test was performed to compare the incidence of overt HE and survival between the different groups, and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models. RESULTS: A total of 108 patients were collected. Among these patients, 45.4% of patients developed overt HE after TIPS treatment. Furthermore, 32.4% and 28.7% of these patients were identified to have myosteatosis and sarcopenia, respectively. Myosteatosis (51.0% vs 16.9%, P < 0.001) and sarcopenia (40.8 vs 18.6%, P = 0.011) were found to be more frequent in patients with overt HE, when compared to patients without overt HE. The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE (AUC = 0.713 and 0.778, respectively) was higher when compared to the neutrophil lymphocyte ratio (AUC = 0.636). The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis, followed by patients with myosteatosis or sarcopenia, while this was the lowest in patients without sarcopenia and myosteatosis. In addition, sarcopenia and myosteatosis were inde-pendently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients. CONCLUSION: CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.

Genomic characteristics of Mycobacterium tuberculosis isolates of cutaneous tuberculosis.

Objectives: Cutaneous tuberculosis with various manifestations can be divided into several clinical types according to the host's immune status and infective route. However, the etiological factors of this disease remain unclear. The objective of this study is to investigate the pathogens associated with the occurrence and different types of cutaneous tuberculosis. Methods: 58 Mycobacterium tuberculosis strains isolated from cutaneous tuberculosis over the last 20 years were sequenced and analyzed for genomic characteristics including lineage distribution, drug-resistance mutations, and mutations potentially associated with different sites of infection. Results: The M. tuberculosis strains from four major types of cutaneous tuberculosis and pulmonary tuberculosis shared similar genotypes and genomic composition. The strains isolated from cutaneous tuberculosis had a lower rate of drug resistance. Phylogenic analysis showed cutaneous tuberculosis and pulmonary tuberculosis isolates scattered on the three. Several SNPs in metabolism related genes exhibited a strong correlation with different infection sites. Conclusions: The different infection sites of TB may barely be affected by large genomic changes in M. tuberculosis isolates, but the significant difference in SNPs of drug resistance gene and metabolism-related genes still deserves more attention.

Multifunctional Nanoprobe Based on Fluorescence Resonance Energy Transfer for Furin Detection and Drug Delivery.

Triple-negative breast cancer is particularly difficult to treat because of its high degree of malignancy and poor prognosis. A fluorescence resonance energy transfer (FRET) nanoplatform plays a very important role in disease diagnosis and treatment due to its unique detection performance. Combining the properties of agglomeration-induced emission fluorophore and FRET pair, a FRET nanoprobe (HMSN/DOX/RVRR/PAMAM/TPE) induced by specific cleavage was designed. First, hollow mesoporous silica nanoparticles (HMSNs) were used as drug carriers to load doxorubicin (DOX). HMSN nanopores were coated with the RVRR peptide. Then, polyamylamine/phenylethane (PAMAM/TPE) was combined in the outermost layer. When Furin cut off the RVRR peptide, DOX was released and adhered to PAMAM/TPE. Finally, the TPE/DOX FRET pair was constituted. The overexpression of Furin in the triple-negative breast cancer cell line (MDA-MB-468 cell) can be quantitatively detected by FRET signal generation, so as to monitor cell physiology. In conclusion, the HMSN/DOX/RVRR/PAMAM/TPE nanoprobes were designed to provide a new idea for the quantitative detection of Furin and drug delivery, which is conducive to the early diagnosis and treatment of triple-negative breast cancer.

The alternative path for fossil oil: Electric vehicles or hydrogen fuel cell vehicles?

New energy vehicles are accelerating to substitute for internal combustion engine vehicles (ICEVs) and fossil oil. Although most literature acknowledges this trend, few compare two specific substitutable paths in terms of the operation system, namely electric vehicles (EVs) and hydrogen fuel cell vehicles (HFCVs). This paper makes a comparative analysis of EVs and HFCVs in power sources, fuel storage and transportation, fuel supply infrastructure construction, and the cost and use of vehicles. Our findings indicate that electric passenger vehicles have more advantages in economy, safety, and environmental impact, in comparison with hydrogen fuel cell passenger vehicles. Nevertheless, great efforts should still be made to develop advanced rapid charging technology, shorten charging time, and accelerate charging infrastructure construction. Then, it is just around the corner for EVs to gradually take over from traditional motor vehicles driven by oil. In contrast, popularizing hydrogen fuel cell passenger vehicles faces several insurmountable obstacles in the short run, such as the high hydrogen production price, complicated storage process, and expensive hydrogen refueling station infrastructure. However, hydrogen fuel cell commercial vehicles have unique application scenarios. The dislocation and complementarity principle in different scenarios of EVs and HFCVs is supposed to be firmly grasped.

Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Weighted BATS Codes with LDPC Precoding.

Batched Sparse (BATS) codes are a type of network coding scheme that use a combination of random linear network coding (RLNC) and fountain coding to enhance the reliability and efficiency of data transmission. In order to achieve unequal error protection for different data, researchers have proposed unequal error protection BATS (UEP-BATS) codes. However, current UEP-BATS codes suffer from high error floors in their decoding performance, which restricts their practical applications. To address this issue, we propose a novel UEP-BATS code scheme that employs a precoding stage prior to the weighted BATS code. The proposed precoding stage utilizes a partially regular low-density parity-check (PR-LDPC) code, which helps to mitigate the high error floors in the weighted BATS code We derive the asymptotic performance of the proposed scheme based on density evolution (DE). Additionally, we propose a searching algorithm to optimize precoding degree distribution within the complexity range of the precoding stage. Simulation results show that compared to the conventional weighted BATS codes, our proposed scheme offers superior UEP performance and lower error floor, which verifies the effectiveness of our scheme.