A sequential macrophage activation strategy for bone regeneration: A micro/nano strontium-releasing composite scaffold loaded with lipopolysaccharide.

Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.

Preliminary construction of a microecological evaluation model for uranium-contaminated soil.

With the extensive development of nuclear energy, soil uranium contamination has become an increasingly prominent problem. The development of evaluation systems for various uranium contamination levels and soil microhabitats is critical. In this study, the effects of uranium contamination on the carbon source metabolic capacity and microbial community structure of soil microbial communities were investigated using Biolog microplate technology and high-throughput sequencing, and the responses of soil biochemical properties to uranium were also analyzed. Then, ten key biological indicators as reliable input variables, including arylsulfatase, biomass nitrogen, metabolic entropy, microbial entropy, Simpson, Shannon, McIntosh, Nocardioides, Lysobacter, and Mycoleptodisus, were screened by random forest (RF), Boruta, and grey relational analysis (GRA). The optimal uranium-contaminated soil microbiological evaluation model was obtained by comparing the performance of three evaluation methods: partial least squares regression (PLS), support vector regression (SVR), and improved particle algorithm (IPSO-SVR). Consequently, partial least squares regression (PLS) has a higher R2 (0.932) and a lower RMSE value (0.214) compared to the other. This research provides a new evaluation method to describe the relationship between soil ecological effects and biological indicators under nuclear contamination.

Disorganized adrenocortical zonational structure in COVID-19 patients: Implications of critical illness duration.

Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.

NSP6 inhibits the production of ACE2-containing exosomes to promote SARS-CoV-2 infectivity.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others' works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural protein 6 (NSP6) inhibits the production of ACE2-exos by affecting the protein level of ACE2 as well as tetraspanin-CD63 which is a key factor for exosome biogenesis. We further found that the protein stability of CD63 and ACE2 is maintained by the deubiquitination of proteasome 26S subunit, non-ATPase 12 (PSMD12). NSP6 interacts with PSMD12 and counteracts its function, consequently promoting the degradation of CD63 and ACE2. As a result, NSP6 diminishes the antiviral efficacy of ACE2-exos and facilitates the virus to infect healthy bystander cells. Overall, our study provides a valuable target for the discovery of promising drugs for the treatment of coronavirus disease 2019. IMPORTANCE: The outbreak of coronavirus disease 2019 (COVID-19) severely endangers global public health. The efficacy of vaccines and antibodies declined with the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants. Angiotensin-converting enzyme 2-containing exosomes (ACE2-exos) therapy exhibits a broad neutralizing activity, which could be used against various viral mutations. Our study here revealed that SARS-CoV-2 nonstructural protein 6 inhibited the production of ACE2-exos, thereby promoting viral infection to the adjacent bystander cells. The identification of a new target for blocking SARS-CoV-2 depends on fully understanding the virus-host interaction networks. Our study sheds light on the mechanism by which the virus resists the host exosome defenses, which would facilitate the study and design of ACE2-exos-based therapeutics for COVID-19.

Engineering a hierarchically micro-/nanostructured Si@Au-based artificial enzyme with improved accessibility of active sites for enhanced catalysis.

The active site accessibility and high loading of gold nanoparticles (AuNPs) are key factors affecting the catalytic activity of supported AuNP-based catalysts. However, the preparation of supported AuNP-based catalysts with highly accessible active sites still remains a challenge. Herein, sphere-on-sphere (SoS) silica microspheres with a hierarchical structure, good dispersion and high surface density of thiol groups (10 SH nm-2) are prepared and used as a platform for the growth of high-density AuNPs. The obtained hierarchical Si@Au micro-/nanostructure consisting of 0.55 µm SoS silica microspheres and 7.3 nm AuNPs (SoS-0.55@Au-7.3) is found to show excellent peroxidase-mimicking activity (Km = 0.033 mM and Vmax = 34.6 × 10-8 M s-1) with merits of high stability and good reusability. Furthermore, the as-obtained SoS-0.55@Au-7.3-based system can sensitively detect hydrogen peroxide (H2O2) with a low detection limit of 1.6 µM and a wide linear range from 2.5 µM to 1.0 mM. The high catalytic activity, excellent stability and good reusability of SoS-0.55@Au-7.3 imply its great prospects in biosensing and biomedical analysis.

Autopsy analysis reveals increased macrophage infiltration and cell apoptosis in COVID-19 patients with severe pulmonary fibrosis.

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.

Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein.

Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).

Sequential Dual-Biofactor Release from the Scaffold of Mesoporous HA Microspheres and PLGA Matrix for Boosting Endogenous Bone Regeneration.

The combined design of scaffold structure and multi-biological factors is a prominent strategy to promote bone regeneration. Herein, a composite scaffold of mesoporous hydroxyapatite (HA) microspheres loaded with the bone morphogenetic protein-2 (BMP-2) and a poly(DL-lactic-co-glycolic acid) (PLGA) matrix is constructed by 3D printing. Furthermore, the chemokine stromal cell-derived factor-1α (SDF-1α) is adsorbed on a scaffold surface to achieve the sequential release of the dual-biofactors. The results indicate that the rapid release of SDF-1α chemokine on the scaffold surface effectively recruits bone marrow-derived mesenchymal stem cells (BMSCs) to the target defect area, whereas the long-term sustained release of BMP-2 from the HA microspheres in the degradable PLGA matrix successfully triggers the osteogenic differentiation in the recruited BMSCs, significantly promoting bone regeneration and reconstruction. In addition, these structures/biofactors specially combining scaffold exhibit significantly better biological performance than that of other combined scaffolds, including the bare HA/PLGA scaffold, the scaffold loaded with SDF-1α or BMP-2 biofactor alone, and the scaffold with surface SDF-1α and BMP-2 dual-biofactors. The utilization of mesoporous HA, the assembly method, and sequential release of the two biofactors in the 3D printed composite scaffold present a new method for future design of high-performance bone repairing scaffolds.

Plant-Derived Polyphenol and LL-37 Peptide-Modified Nanofibrous Scaffolds for Promotion of Antibacterial Activity, Anti-Inflammation, and Type-H Vascularized Bone Regeneration.

The regeneration of oral tissues is a challenging clinical problem because of the complex microbial and biological stress environments. Electrospun fibrous scaffolds have attracted significant interest as effective barrier membranes for guided bone regeneration (GBR); however, no mature strategy yet exists for the surface modification of fibers to provide versatility to satisfy clinical requirements. This study demonstrated a practical biosafety strategy: the combined use of plant polyphenols and LL-37 peptides to modify the fiber surface to endow the fibrous scaffold with antimicrobial activity, immunoregulation, and vascularized bone regeneration. We confirmed that the LL-37 peptides interacted with tannic acid (TA) through noncovalent bonds through experiments and molecular docking simulation analysis. In vitro experiments showed that the TA coating imparted strong antibacterial properties to the fibrous scaffold, but it also caused cytotoxicity. The grafting of LL-37 peptide promoted the spreading, migration, and osteogenic differentiation of mesenchymal stem cells and was also conducive to the M2 polarization of RAW264.7 cells. In vivo experiments further verified that the LL-37 peptide-grafted fibrous scaffold significantly enhanced angiogenesis, anti-inflammatory effects, and type-H vascularized bone regeneration. Overall, the fibrous scaffold modified by the LL-37 peptide through TA grafting has significant potential for GBR applications.

Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice.

Despite numerous advances in tuberculosis (TB) drug development, long treatment durations have led to the emergence of multidrug resistance, which poses a major hurdle to global TB control. Shortening treatment time therefore remains a top priority. Host-directed therapies that promote bacterial clearance and/or lung health may improve the efficacy and treatment duration of tuberculosis antibiotics. We recently discovered that inhibition of the integrated stress response, which is abnormally activated in tuberculosis and associated with necrotic granuloma formation, reduced bacterial numbers and lung inflammation in mice. Here, we evaluated the impact of the integrated stress response (ISR) inhibitor ISRIB, administered as an adjunct to standard tuberculosis antibiotics, on bacterial clearance, relapse, and lung pathology in a mouse model of tuberculosis. Throughout the course of treatment, ISRIB robustly lowered bacterial burdens compared to the burdens with standard TB therapy alone and accelerated the time to sterility in mice, as demonstrated by significantly reduced relapse rates after 4 months of treatment. In addition, mice receiving adjunctive ISRIB tended to have reduced lung necrosis and inflammation. Together, our findings identify the ISR pathway as a promising therapeutic target with the potential to shorten TB treatment durations and improve lung health. IMPORTANCE Necrosis of lung lesions is a hallmark of tuberculosis (TB) that promotes bacterial growth, dissemination, and transmission. This process is driven by the persistent hyperactivation of the integrated stress response (ISR) pathway. Here, we show that adjunctive ISR inhibition during standard antibiotic therapy accelerates bacterial clearance and reduces immunopathology in a clinically relevant mouse model of TB, suggesting that host-directed therapies that de-escalate these pathological stress responses may shorten TB treatment durations. Our findings present an important conceptual advance toward overcoming the challenge of improving TB therapy and lowering the global burden of disease.

Chemical composition of kabuli and desi chickpea (Cicer arietinum L.) cultivars grown in Xinjiang, China.

Chickpeas are a very important legume crop and have abundant protein, carbohydrate, lipid, fiber, isoflavone, and mineral contents. The chemical compositions of the four chickpea species (Muying-1, Keying-1, Desi-1, Desi-2) from Xinjiang, China, were analyzed, and 46 different flavonoids in Muying-1 were detected. The moisture content ranged from 7.64 ± 0.01 to 7.89 ± 0.02 g/100 g, the content of starch in the kabuli chickpeas was greater than that in the desi chickpeas, the total ash content ranged from 2.59 ± 0.05 to 2.69 ± 0.03 g/100 g and the vitamin B1 content of the chickpeas ranged from 0.31 to 0.36 mg/100 g. The lipid content ranged from 6.35 to 9.35 g/100 g and the major fatty acids of chickpeas were linoleic, oleic, and palmitic acids. Both kabuli and desi chickpeas have a high content of unsaturated fatty acids (USFAs), Muying-1 and Desi-1 contained the highest level of linoleic acid, and Keying-1 had the highest oleic acid content. The protein level ranged from 19.79 ± 2.89 to 23.38 ± 0.30 g/100 g, and the main amino acids were aspartic acid, glutamic acid, and arginine acid. The four chickpea species had significant amounts of essential amino acids (EAAs). Forty-six varieties of flavonoids in Muying-1 were determined by ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS) analysis, and there were higher levels of conjugate flavonoids (55.95%) than free flavonoids (44.05%). Isoflavones were the most abundant flavonoids in Muying-1, and among the isoflavones, daidzin had the highest content, followed by biochanin A and genistin. Muying-1 was rich in daidzin, biochanin A, genistin, troxerutin, isorhamnetin, astilbin, L-epicatechin, astragalin, acacetin, hyperoside, and myricitrin. Information provided in the study will be helpful to further understand the chemical composition of chickpeas and be beneficial to the development of chickpeas.

Strontium and simvastatin dual loaded hydroxyapatite microsphere reinforced poly(ε-caprolactone) scaffolds promote vascularized bone regeneration.

The promotion of vascular network formation in the early stages of implantation is considered a prerequisite for successful functional bone regeneration. In this study, we successfully constructed 3D printed scaffolds with strong mechanical strength and a controllable pore structure that can sustainably release strontium (Sr) ions and simvastatin (SIM) for up to 28 days by incorporation of Sr2+ and SIM-loaded hydroxyapatite microspheres (MHA) into a poly(ε-caprolactone) (PCL) matrix. In vitro cell experiments showed that Sr-doped scaffolds were beneficial to the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), an appropriate dose of SIM was beneficial to cell proliferation and angiogenesis, and a high dose of SIM was cytotoxic. The Sr- and SIM-dual-loaded scaffolds with an appropriate dose significantly induced osteogenic differentiation of BMSCs and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and promoted vascular network and functional bone formation in vivo. Ribose nucleic acid (RNA) sequencing analysis suggested that the mechanism of promotion of vascularized bone regeneration by fabricated scaffolds is that dual-loaded Sr2+ and SIM can upregulate osteogenic and vasculogenic-related genes and downregulate osteoclast-related genes, which is beneficial for vascular and new bone regeneration. The 3D printed composite scaffolds loaded with high-stability and low-cost inorganic Sr2+ ions and SIM small-molecule drugs hold great promise in the field of promoting vascularized bone regeneration.

Therapeutic potential of coumestan Pks13 inhibitors for tuberculosis.

Polyketide synthase 13 (Pks13) is an important enzyme found in Mycobacterium tuberculosis (M. tuberculosis) that condenses two fatty acyl chains to produce α-alkyl ß-ketoesters, which in turn serve as the precursors for the synthesis of mycolic acids that are essential building blocks for maintaining the cell wall integrity of M. tuberculosis Coumestan derivatives have recently been identified in our group as a new chemotype that exert their antitubercular effects via targeting of Pks13. These compounds were active on both drug-susceptible and drug-resistant strains of M. tuberculosis as well as showing low cytotoxicity to healthy cells and a promising selectivity profile. No cross-resistance was found between the coumestan derivatives and first-line TB drugs. Here we report that treatment of M. tuberculosis bacilli with 15 times the MIC of compound 1, an optimized lead coumestan compound, resulted in a colony forming unit (CFU) reduction from 6.0 log10 units to below the limit of detection (1.0 log10 units) per mL culture, demonstrating a bactericidal mechanism of action. Single dose (10 mg/kg) pharmacokinetic studies revealed favorable parameters with a relative bioavailability of 19.4%. In a mouse infection and chemotherapy model, treatment with 1 showed dose-dependent mono-therapeutic activity, whereas treatment with 1 in combination with rifampin showed clear synergistic effects. Together these data suggest that coumestan derivatives are promising agents for further TB drug development.

Nanoparticles and Antiviral Vaccines.

Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines.

A tandem CCCH type zinc finger protein gene CpC3H3 from Chimonanthus praecox promotes flowering and enhances drought tolerance in Arabidopsis.

BACKGROUND: CCCH-type zinc finger proteins play important roles in plant development and biotic/abiotic stress responses. Wintersweet (Chimonanthus praecox) is a popular ornamental plant with strong resistance to various stresses, which is a good material for exploring gene resource for stress response. In this study, we isolated a CCCH type zinc finger protein gene CpC3H3 (MZ964860) from flower of wintersweet and performed functional analysis with a purpose of identifying gene resource for floral transition and stress tolerance. RESULTS: CpC3H3 was predicted a CCCH type zinc finger protein gene encoding a protein containing 446 amino acids with five conserved C-X8-C-X5-C-X3-H motifs. CpC3H3 was localized in the cell membrane but with a nuclear export signal at the N-terminal. Transcripts of CpC3H3 were significantly accumulated in flower buds at floral meristem formation stage, and were induced by polyethylene glycol. Overexpression of CpC3H3 promoted flowering, and enhanced drought tolerance in transgenic A. thaliana. CpC3H3 overexpression affects the expression level of genes involved in flower inducement and stress responses. Further comparative studies on physiological indices showed the contents of proline and soluble sugar, activity of peroxidase and the rates of electrolyte leakage were significantly increased and the content of malondialdehyde and osmotic potential was significantly reduced in transgenic A. thaliana under PEG stress. CONCLUSION: Overall, CpC3H3 plays a role in flowering inducement and drought tolerance in transgenic A. thaliana. The CpC3H3 gene has the potential to be used to promote flowering and enhance drought tolerance in plants.

Ameliorative effects of chickpea flavonoids on redox imbalance and mitochondrial complex I dysfunction in type 2 diabetic rats.

Chickpeas are an important source of flavonoids in the human diet, and researchers have demonstrated that flavonoids have antidiabetic compositions in chickpeas. Because the NAD+/NADH redox balance is heavily perturbed in diabetes and complex I is the only site for NADH oxidation and NAD+ regeneration, in the present study, mitochondrial complex I was used as a target for anti-diabetes. The objective of this study was to investigate the effects of a crude chickpea flavonoid extract (CCFE) on NAD+/NADH redox imbalance and mitochondrial complex I dysfunction in the pancreas as well as oxidative stress in type 2 diabetes mellitus (T2DM) rats. Our results demonstrated that the degree of NAD+/NADH redox imbalance in the pancreas of T2DM rats was alleviated by CCFE, which is likely attributed to the inhibition of the polyol pathway and the decrease in poly ADP ribose polymerase (PARP) and sirtuin 3 (Sirt3) activities. Moreover, mitochondrial complex I dysfunction in the pancreas of T2DM rats was ameliorated by CCFE through the suppression of the activity of complex I. Furthermore, CCFE treatment could attenuate oxidative stress in T2DM rats, which was proven by the reduction in hydrogen peroxide (H2O2) and malondialdehyde (MDA) as well as the upregulation of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in serum. CCFE treatment significantly improved dyslipidemia in T2DM rats.

Association Between Passive Smoking and Menstrual Discomfort: A Cross-Sectional Study of 2,571 Non-smoking Chinese Nurses.

Introduction: Menstrual discomfort affects women's quality of life, which is an important public health issue. Evidence confirming the link between passive smoking and menstrual discomfort is limited. Therefore, the aim of this study is to investigate the aforementioned topic on the basis of a cross-sectional study of 2,571 non-smoking Chinese nurses. Methods: Demographic information and passive smoking were assessed using a self-administered questionnaire. Menstrual discomfort was characterized as dysmenorrhea, illness or weakness, bed rest, and restlessness during menstruation, which was assessed using a modified version of the Cornell Medical Index-Health Questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CIs) were estimated using the logistic regression model. Results: A total of 1:195 nurses (46.48%) were exposed to passive smoking. Compared with non-passive smoking nurses, passive smoking nurses were more likely to have menstrual discomfort symptoms (72.38 vs. 64.39%), especially symptoms of dysmenorrhea (49.54 vs. 42.08%), illnesses or weakness (48.28 vs. 42.08%), and restlessness during menstruation (53.05 vs. 46.22%). Exposure to passive smoking was significantly associated with menstrual discomfort (OR = 1.41, 95%CI: 1.19-1.67), especially symptoms of dysmenorrhea (OR = 1.32, 95%CI: 1.13-1.56), illness or weakness (OR = 1.24, 95%CI: 1.06-1.46), and restlessness (OR = 1.26, 95%CI: 1.08-1.48) during menstruation. The subgroup analyses, stratified by age, children, and marital status, agreed with the main findings. Conclusions: Exposure to passive smoking was related to symptoms of dysmenorrhea and menstrual discomfort.

Biochar-based microbial agent reduces U and Cd accumulation in vegetables and improves rhizosphere microecology.

Microbial remediation of heavy metals in soil has been widely studied. However, bioremediation efficiency is limited in practical applications because of nutritional deficiency, low efficiency, and competition with indigenous microorganisms. Herein, we prepared a biochar-based microbial agent (BMA) by immobilizing the microbial agent (MA, containing Bacillus subtilis, Bacillus cereus, and Citrobacter sp.) on biochar for the remediation of U and Cd in soil. The results showed that BMA increased soil organic matter, cation exchange capacity, and fluorescein diacetate hydrolysis activity and dehydrogenase activity by 58.7%, 38.2%, 42.9%, and 51.1%. The availability of U and Cd were significantly decreased by 67.4% and 54.2% in BMA amended soil, thereby reducing their accumulation in vegetables. BMA greatly promoted vegetable growth. Additionally, BMA significantly altered the structure and function of rhizosphere soil microbial communities. Coincidently, more abundant ecologically beneficial bacteria like Nitrospira, Nitrosomonas, Lysobacter, and Bacillus were observed, whereas plant pathogenic fungi like Fusarium and Alternaria reduced in BMA amended soil. The network analysis revealed that BMA amendment increased the tightness and complexity of microbial communities. Importantly, the compatibility of niches and microbial species within co-occurrence network was enhanced after BMA addition. These findings provide a promising strategy for suppressing heavy metal accumulation in vegetables and promoting their growth.

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

A single-cell transcriptomic landscape of the lungs of patients with COVID-19.

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.