Sex disparities of the effect of the COVID-19 pandemic on mortality among patients living with tuberculosis in the United States.

Background: We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic. Methods: TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic. Results: A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%). Conclusion: The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic.

Ensemble learning algorithms to elucidate the core microbiome's impact on carbon content and degradation properties at the soil aggregate level.

Soil aggregates are crucial for soil organic carbon (OC) accumulation. This study, utilizing a 32-year fertilization experiment, investigates whether the core microbiome can elucidate variations in carbon content and decomposition across different aggregate sizes more effectively than broader bacterial and fungal community analyses. Employing ensemble learning algorithms that integrate machine learning with network inference, we found that the core microbiome accounts for an average increase of 26 % and 20 % in the explained variance of PCoA and Adonis analyses, respectively, in response to fertilization. Compared to the control, inorganic and organic fertilizers decreased the decomposition index (DDI) by 31 % and 38 %, respectively. The fungal core microbiome predominantly influenced OC content and DDI in larger macroaggregates (>2000 µm), explaining over 35 % of the variance, while the bacterial core microbiome had a lesser impact, explaining <30 %. Conversely, in smaller aggregates (<2000 µm), the bacterial core microbiome significantly influenced DDI (R2 > 0.2), and the fungal core microbiome more strongly affected OC content (R2 > 0.3). Mantel tests showed that pH is the most significant environmental factor affecting core microbiome composition across all aggregate sizes (Mantel's r > 0.8, P < 0.01). Linear correlation analysis further confirmed that the core microbiome's community structure could accurately predict OC content and DDI in aggregates (R2 > 0.8, P < 0.05). Overall, our findings suggested that the core microbiome provides deeper insights into the variability of aggregate organic carbon content and decomposition, with the bacterial core microbiome playing a particularly pivotal role within the soil aggregates.

Stem cell division and its critical role in mammary gland development and tumorigenesis: current progress and remaining challenges.

The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells (MaSCs) and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetric cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of breast cancer stem cells (BCSCs) division modes and cause BC. Important regulatory factors such as mammalian Inscuteable (mInsc), Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.

Moderation Effects of Daily Behavior on Associations Between Symptoms and Social Participation Outcomes After Burn Injury: A 6-Month Digital Phenotyping Study.

OBJECTIVE: To examine the moderation effects of daily behavior on the associations between symptoms and social participation outcomes after burn injury. DESIGN: A 6-month prospective cohort study. SETTING: Community. PARTICIPANTS: Twenty-four adult burn survivors. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Symptoms and social participation outcomes were assessed weekly using smartphone surveys, including symptoms of pain (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Intensity and Pain Interference), anxiety (PROMIS Anxiety), and depression (Patient Health Questionnaire), as well as outcomes of social interactions and social activities (Life Impact Burn Recovery Evaluation [LIBRE] Social Interactions and Social Activities). Daily behaviors were automatically recorded by a smartphone application and smartphone logs, including physical activity (steps, travel miles, and activity minutes), sleep (sleep hours), and social contact (number of phone calls and message contacts). RESULTS: Multilevel models controlling for demographic and burn injury variables examined the associations between symptoms and social participation outcomes and the moderation effects of daily behaviors. Lower (worse) LIBRE Social Interactions and LIBRE Social Activities scores were significantly associated with higher (worse) PROMIS Pain Intensity, PROMIS Pain Interference, PROMIS Anxiety, and Patient Health Questionnaire-8 scores (P<.05). Additionally, daily steps and activity minutes were associated with LIBRE Social Interactions and LIBRE Social Activities (P<.05), and significantly moderated the association between PROMIS Anxiety and LIBRE Social Activities (P<.001). CONCLUSIONS: Social participation outcomes are associated with pain, anxiety, and depression symptoms after burn injury, and are buffered by daily physical activity. Future intervention studies should examine physical activity promotion to improve social recovery after burns.

Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model.

Objective: This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans (C. elegans). Methods: In this study, the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C. elegans. The worms were fed Escherichia coli OP50 ( E. coli OP50), glucose, and different concentrations of LFBEP-C1. Body size, lifespan, movement, triglyceride content, and gene expression were analyzed. The results were analyzed using ANOVA and Tukey's multiple comparison test. Results: Compared with the model group, the head-swing frequency of C. elegans in the group of LFBEP-C1 at 20 µg/mL increased by 33.88%, and the body-bending frequency increased by 27.09%. This indicated that LFBEP-C1 improved the locomotive ability of C. elegans. The average lifespan of C. elegans reached 13.55 days, and the body length and width of the C. elegans decreased after LFBEP-C1 intake. Additionally, LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels. The expression levels of sbp-1, daf-2, and mdt-15 significantly decreased, while those of daf-16, tph-1, mod-1, and ser-4 significantly increased after LFBEP-C1 intake. Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion: LFBEP-C1 significantly reduced lipid deposition in C. elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development, lifespan, and exercise behavior of C. elegans. In addition, LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein, insulin, and 5-hydroxytryptamine signaling pathways.

Chondrocyte autophagy mediated by T-2 toxin via AKT/TSC/Rheb/mTOR signaling pathway and protective effect of CSA-SeNP.

OBJECTIVE: Kashin-Beck disease (KBD) is an endemic, degenerative, and cartilage-damaging disease for which low selenium and T-2 toxins are considered environmental pathogenic factors. This study aimed to investigate the molecular mechanisms of autophagy in cartilage damage caused by T-2 toxin and the protective effect of chondroitin sulfate A nano-elemental selenium (CSA-SeNP) on the cartilage. METHODS: KBD chondrocytes and C28/I2 human chondrocyte cell lines were used. T-2 toxin, AKT inhibitor, and CSA-SeNP treatment experiments were conducted separately, with a treatment time of 24 h. Autophagy was monitored using MDC staining, and mRFP-GFP-LC3 adenovirus, respectively. RT-qPCR and western blotting were used to detect the expression of the relevant genes and proteins. RESULTS: The suppression of autophagy observed in KBD chondrocytes was replicated by applying 10 ng/mL T-2 toxin to C28/I2 chondrocytes for 24 h. The AKT/TSCR/Rheb/mTOR signaling pathway was activated by T-2 toxin, which inhibits autophagy. The supplementation with CSA-SeNP alleviated the inhibition of autophagy by T-2 toxin through the AKT/TSCR/Rheb/mTOR signaling pathway. CONCLUSIONS: Loss of autophagy regulated by the AKT/TSCR/Rheb/mTOR signaling pathway plays an important role in cartilage damage caused by T-2 toxin. CSA-SeNP supplementation attenuated inhibition of autophagy in chondrocytes by T-2 toxin by modulating this signaling pathway. These findings provide promising new targets for the prevention and treatment of cartilage disease.

Low selenium and T-2 toxin may be involved in the pathogenesis of Kashin-Beck disease by affecting AMPK/mTOR/ULK1 pathway mediated autophagy.

Kashin-Beck disease (KBD) is an endemic, environmentally associated cartilage disease. Previous studies have shown that the environmental suspected pathogenic factors of KBD, T-2 toxin and low selenium, are involved in the regulation of inflammation, oxidative stress and autophagy in some tissues and organs. In cartilage diseases, the level of cellular autophagy determines the fate of the chondrocytes. However, whether autophagy is involved in KBD cartilage lesions, and the role of low selenium and T-2 toxins in KBD cartilage injury and autophagy are still unclear. This work took the classical AMPK/mTOR/ULK1 autophagy regulatory pathway as the entry point to clarify the relationship between the environmental suspected pathogenic factors and chondrocyte autophagy. Transmission electron microscopy was used to observe the autophagy of chondrocytes in KBD patients. qRT-PCR and western blot were used to analyze the expression of AMPK/mTOR/ULK1 pathway and autophagy markers. The rat model of KBD was established by low selenium and T-2 toxin, the autophagy in rat cartilage was detected after 4- and 12-week interventions. Chondrocyte autophagy was found in KBD, and the AMPK/mTOR/ULK1 pathway was down-regulated. In the rat model, the pathway showed an up-regulated trend when low selenium and T-2 toxin, were treated for a short time or low concentration, and autophagy level increased. However, when low selenium and T-2 toxin were treated for a long time or at high concentrations, the pathway showed a down-regulated trend, and the autophagy level was reduced and even defective. In conclusion, in the process of KBD cartilage lesion, chondrocyte autophagy level may increase in the early stage, and decrease in the late stage with the progression of lesion. Low selenium and T-2 toxins may affect autophagy by AMPK/mTOR/ULK1 pathway.

An untargeted metabolomics study of cardiac pathology damage in rats caused by low selenium diet alone or in combination with T-2 toxin.

T-2 toxin is a highly cardiotoxic environmental contaminant. Selenium can uphold the cardiovascular system's functionality. Selenium insufficiency is common. The aim of this study was to elucidate the effects of low selenium diet alone or in combination with T-2 toxin on myocardial tissue damage. Thirty-two Sprague-Dawley rats of 3 weeks of age were randomized into control, low selenium diet, low selenium diet combined with T-2 toxin groups (at doses of 10 ng/g and 100 ng/g body weight) for 12-weeks intervention. Pathohistology and ultrastructural changes in cardiac tissue were observed. Changes in cardiac metabolites were analyzed using untargeted metabolomics. The findings demonstrated that cardiac tissue abnormalities, interstitial bleeding, inflammatory cell infiltration, and mitochondrial damage can be brought on by low selenium diet alone or in combination with the T-2 toxin. A low selenium diet alone or in combination with the T-2 toxin affected cardiac metabolic profiles and resulted in aberrant modifications in many metabolic pathways, including the metabolism of amino acids, cholesterol, and thiamine. Accordingly, low selenium diet and T-2 toxin may have a synergistic effect. Our findings provide fresh insights into the processes of cardiac injury by revealing the effects of low selenium diet and T-2 toxin on cardiac metabolism.

The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.

Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.

Interactions between MDSCs and the Autonomic Nervous System: Opportunities and Challenges in Cancer Neuroscience.

Myeloid-derived suppressor cells (MDSC) are a population of heterogeneous immune cells that are involved in precancerous conditions and neoplasms. The autonomic nervous system (ANS), which is composed of the sympathetic nervous system and the parasympathetic nervous system, is an important component of the tumor microenvironment that responds to changes in the internal and external environment mainly through adrenergic and cholinergic signaling. An abnormal increase of autonomic nerve density has been associated with cancer progression. As we discuss in this review, growing evidence indicates that sympathetic and parasympathetic signals directly affect the expansion, mobilization, and redistribution of MDSCs. Dysregulated autonomic signaling recruits MDSCs to form an immunosuppressive microenvironment in chronically inflamed tissues, resulting in abnormal proliferation and differentiation of adult stem cells. The two components of the ANS may also be responsible for the seemingly contradictory behaviors of MDSCs. Elucidating the underlying mechanisms has the potential to provide more insights into the complex roles of MDSCs in tumor development and lay the foundation for the development of novel MDSC-targeted anticancer strategies.

Determination of 10 mycotoxins in wine, baijiu, and huangjiu of the Chinese market by liquid chromatography tandem mass spectrometry and exposure estimation.

In this study, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to analyze the prevalence of 10 mycotoxins in 140 samples from the Chinese market, aiming to assess the exposure of Chinese individuals to these mycotoxins through the consumption of wine, baijiu, and huangjiu. Mycotoxins were detected in 98% of the samples, with fumonisins (FBs), deoxynivalenol (DON), and zearalenone (ZEN) exhibiting positive rates exceeding 50%. Regarding the exposure of the Chinese population to mycotoxins resulting from alcoholic beverage consumption, fruit wine intake made a relatively significant contribution to aflatoxin exposure, while baijiu showed a relatively significant contribution to ZEN exposure (1.84%). The analysis of the correlation between grape variety, wine region, and mycotoxin content demonstrated that FBs, ZEN, and DON were significantly influenced by grape variety and wine region. This research holds great significance in protecting human life and health, as well as in the production of safer alcoholic beverages.

Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of 10 mycotoxins in beer of the Chinese market and exposure estimate.

Mycotoxins are important risk factors in beer. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine 10 mycotoxins in beer within 6 min. The method is fast, efficient, and has a simple and quick sample preparation. Validation was conducted based on the performance standards specified in Commission Decision 657/2002/EC, and the results demonstrated excellent linearity (R2 > 0.99), repeatability (RSD < 5 %), quantification limits (0.005-20.246 µg/L), and recovery rates (77 %-118 %). The prevalence of the 10 mycotoxins in 96 beers purchased from the Chinese market was analyzed, and the exposure of the Chinese population to mycotoxins through beer consumption was assessed. Deoxynivalenol (DON) was detected in 93.75 % of the beers, and the incidence of fumonisins (FBs) and zearalenone (ZEN) exceeded 50 %. Beer intake contributed significantly to the exposure of aflatoxins (AFs) and DON, especially in males. Correlation analysis between mycotoxin content in beer, raw materials, and the brewing process revealed that the brewing process significantly affected the content of DON (P < 0.001), while auxiliary materials also had a significant impact on the content of FBs and DON (P < 0.001). This study holds great significance in producing higher quality and safer beer.

Sub-pixel marking and depth-based correction methods for the elimination of voxel drifting in integral imaging display.

Integral imaging is a kind of true three-dimensional (3D) display technology that uses a lens array to reconstruct vivid 3D images with full parallax and true color. In order to present a high-quality 3D image, it's vital to correct the axial position error caused by the misalignment and deformation of the lens array which makes the reconstructed lights deviate from the correct directions, resulting in severe voxel drifting and image blurring. We proposed a sub-pixel marking method to measure the axial position error of the lenses with great accuracy by addressing the sub-pixels under each lens and forming a homologous sub-pixel pair. The proposed measurement method relies on the geometric center alignment of image points, which is specifically expressed as the overlap between the test 3D voxel and the reference 3D voxel. Hence, measurement accuracy could be higher. Additionally, a depth-based sub-pixel correction method was proposed to eliminate the voxel drifting. The proposed correction method takes the voxel depth into consideration in the correction coefficient, and achieves accurate error correction for 3D images with different depths. The experimental results well confirmed that the proposed measuring and correction methods can greatly suppress the voxel drifting caused by the axial position error of the lenses, and greatly improve the 3D image quality.

Research of wet string grid dust removal vehicle and creation of dust control area on tunnel working face.

The spread of blast dust throughout the tunnel becomes a common problem in drill and blast tunneling,the key to breaking through the problem is the creation of a dust control area on the working face.In view of this key problem, a wet string grid dust removal crawler vehicle was developed, the power of the vehicle came from the diesel generator, and further, the air cooler of the diesel generator was used to generate airflow, and the suction process formed by the on-board axial flow fan was coupled to create a dust control area of the working face after blasting.The results show that when the frequency of the axial flow fan is adjusted to 30 Hz, the airflow speed of the wet chord grid section reaches 3.34 m/s, and the dust removal efficiency is the highest, with a value of 94.3%.Compared with the non-use of the dust removal vehicle, when the air outlet of the air cooler is front, horizontal front, horizontal rear, the dust concentration is reduced by 74.37, 92.39 and 50.53%.Finally, the optimized wet grid dust removal crawler was installed in the Dading tunnel, and the actual dust reduction efficiency was about 78.49%. The results obtained provide an important technical way to improve the working environment of the drilling and blasting construction tunnel.

Remote sensing estimation of regional PM2.5 based on GTWR model -A case study of southwest China.

Air pollution in China has becoming increasingly serious in recent years with frequent incidents of smog. Parts of southwest China still experience high incidents of smog, with PM2.5 (particulate matter with diameter ≤2.5 µm) being the main contributor. Establishing the spatial distribution of PM2.5 in Southwest China is important for safeguarding regional human health, environmental quality, and economic development. This study used remote sensing (RS) and geographical information system (GIS) technologies and aerosol optical depth (AOD), digital elevation model (DEM), normalized difference vegetation index (NDVI), population density, and meteorological data from January to December 2018 for southwest China. PM2.5 concentrations were estimated using ordinary least squares regression (OLS), geographic weighted regression (GWR) and geographically and temporally weighted regression (GTWR). The results showed that: (1) Eight influencing factors showed different correlations to PM2.5 concentrations. However, the R2 values of the correlations all exceeded 0.3, indicating a moderate degree of correlation or more; (2) The correlation R2 values between the measured and remote sensed estimated PM2.5 data by OLS, GWR, and GTWR were 0.554, 0.713, and 0.801, respectively; (3) In general, the spatial distribution of PM2.5 in southwest of China decreases from the Northeast to Northwest, with moderate concentrations in the Southeast and Southwest; (4) The seasonal average PM2.5 concentration is high in winter, low in summer, and moderate in spring and autumn, whereas the monthly average shows a "V" -shaped oscillation change.

CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.

Cancer cell response to extrinsic and intrinsic mechanical cue: opportunities for tumor apoptosis strategies.

Increasing studies have revealed the importance of mechanical cues in tumor progression, invasiveness and drug resistance. During malignant transformation, changes manifest in either the mechanical properties of the tissue or the cellular ability to sense and respond to mechanical signals. The major focus of the review is the subtle correlation between mechanical cues and apoptosis in tumor cells from a mechanobiology perspective. To begin, we focus on the intracellular force, examining the mechanical properties of the cell interior, and outlining the role that the cytoskeleton and intracellular organelle-mediated intracellular forces play in tumor cell apoptosis. This article also elucidates the mechanisms by which extracellular forces guide tumor cell mechanosensing, ultimately triggering the activation of the mechanotransduction pathway and impacting tumor cell apoptosis. Finally, a comprehensive examination of the present status of the design and development of anti-cancer materials targeting mechanotransduction is presented, emphasizing the underlying design principles. Furthermore, the article underscores the need to address several unresolved inquiries to enhance our comprehension of cancer therapeutics that target mechanotransduction.