Competition of Cd(II) and Pb(II) on the bacterial cells: a new insight from bioaccumulation based on NanoSIMS imaging.

Polymetallic exposure causes complex toxicity to microorganisms. In this study, we investigated the responses of Escherichia coli under co-existence of cadmium (Cd) and lead (Pb), primarily based on biochemical analysis and RNA sequencing. Cd completely inhibited bacterial growth at a concentration of 2.41 mmol/L, with its removal rate as low as <10%. In contrast, the Pb removal rate was >95% under equimolar sole Pb stress. In addition, the Raman analysis confirmed the loss of proteins for the bacterial cells. Under the co-existence of Cd and Pb, the Cd toxicity to E. coli was alleviated. Meanwhile, the biosorption of Pb cations was more intense during the competitive sorption with Cd. Transmission electron microscopy images showed that a few cells were elongated during incubation, i.e., the average cellular length increased from 1.535 ± 0.407 to 1.845 ± 0.620 µm. Moreover, NanoSIMS imaging showed that the intracellular distribution of Cd and Pb was coupled with sulfur. Genes regulating sulfate transporter were also upregulated to promote sulfate assimilation. Then, the subsequent production of biogenic sulfide and sulfur-containing amino acids was enhanced. Although this strategy based on S enrichment could resist the polymetallic stress, not all related genes were induced to upregulate under sole Cd stress. Therefore, the S metabolism might remodel the microbial resistance to variable occurrence of heavy metals. Furthermore, the competitive sorption (in contrast to sole Cd stress) could prevent microbial cells from strong Cd toxicity.IMPORTANCEMicrobial tolerance and resistance to heavy metals have been widely studied under stress of single metals. However, the polymetallic exposure seems to prevail in the environment. Though microbial resistance can alleviate the effects of exogenous stress, the taxonomic or functional response to polymetallic exposure is still not fully understood. We determined the strong cytotoxicity of cadmium (Cd) on growth, and cell elongation would be driven by Cd stress. The addition of appropriate lead (Pb) showed a stimulating effect on microbial bioactivity. Meanwhile, the biosorption of Pb was more intense during co-existence of Pb and Cd. Our work also revealed the spatial coupling of intracellular S and Cd/Pb. In particular, the S assimilation was promoted by Pb stress. This work elucidated the microbial responses to polymetallic exposure and may provide new insights into the antagonistic function during metal stresses.

Family history, waist circumference and risk of ischemic stroke: A prospective cohort study among Chinese adults.

BACKGROUND AND AIMS: The associations between genetic factors and waist circumference (WC) with stroke risk have been evaluated in Western studies. However, evidence of this association has rarely been reported in the Chinese population. This study aimed to evaluate the association between WC and family history of stroke (FHS) with ischemic stroke (IS) risk among Chinese adults and to further explore the potential interaction of these associations. METHODS AND RESULTS: The China Kadoorie Biobank (CKB) study recruited 35,508 participants aged 30-79 years from the Qingdao urban area during 2004-2008. A total of 33,355 participants were included in study. Cox regression analysis was used to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the independent and interactional associations between FHS and WC and IS risk. Participants with FHS had a 29% (HR = 1.29, 95% CI: 1.12-1.50) higher IS risk than those without FHS. Participants with excessive WC (85 cm for males and 80 cm for females) had a 78% (HR = 1.78, 95% CI: 1.51-2.10) higher IS risk than those with normal WC. The combined effect of FHS and excessive WC on IS was statistically significant (HR = 2.29, 95% CI: 1.84-2.86). The present study further found statistically significant multiplicative interactions of FHS and WC with IS risk (Pinteraction < 0.001). CONCLUSION: The present study indicated that FHS and WC were significantly associated with an increased risk of IS. The association between FHS and IS was associated with excessive WC.

Decreased gray matter volume and dynamic functional alterations in medicine-free obsessive-compulsive disorder.

BACKGROUND: Previous studies discovered the presence of abnormal structures and functions in the brain regions of patients with obsessive-compulsive disorder (OCD). Nevertheless, whether structural changes in brain regions are coupled with alterations in dynamic functional connectivity (dFC) at rest in medicine-free patients with OCD remains vague. METHODS: Three-dimensional T1-weighed magnetic resonance imaging (MRI) and resting-state functional MRI were performed on 50 medicine-free OCD and 50 healthy controls (HCs). Firstly, the differences in gray matter volume (GMV) between OCD and HCs were compared. Then, brain regions with aberrant GMV were used as seeds for dFC analysis. The relationship of altered GMV and dFC with clinical parameters in OCD was explored using partial correlation analysis. Finally, support vector machine was applied to examine whether altered multimodal imaging data might be adopted to distinguish OCD from HCs. RESULTS: Our findings indicated that GMV in the left superior temporal gyrus (STG) and right supplementary motor area (SMA) was reduced in OCD, and the dFC between the left STG and the left cerebellum Crus I and left thalamus, and between the right SMA and right dorsolateral prefrontal cortex (DLPFC) and left precuneus was decreased at rest in OCD. The brain regions both with altered GMV and dFC values could discriminate OCD from HCs with the accuracy of 0.85, sensitivity of 0.90 and specificity of 0.80. CONCLUSION: The decreased gray matter structure coupling with dynamic function in the left STG and right SMA at rest may be crucial in the pathophysiology of OCD. TRIAL REGISTRATION: Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (registration date: 08/11/2017; registration number: ChiCTR-COC-17,013,301).

Natural exosomes-like nanoparticles in mung bean sprouts possesses anti-diabetic effects via activation of PI3K/Akt/GLUT4/GSK-3ß signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance. Mung bean sprouts are traditionally considered a "folk" hypoglycemic food and their pharmacological effects and underlying mechanisms warrant further investigation. PURPOSE: This study aimed to investigate the anti-diabetic effects of the exosomes-like nanoparticles in mung bean sprouts (MELNs) and explore the related molecular mechanisms. RESULTS: MELNs were isolated using a differential centrifugation-polyethylene glycol (PEG) method, and the identification of MELNs were confirmed by PAGE gel electrophoresis, agarose gel electrophoresis, thin-layer chromatography (TLC), and transmission electron microscopy (TEM). In the high-fat diet/streptozotocin (HFD/STZ) mouse model, MELNs ameliorated the progression of T2DM by increasing oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results, decreasing the fasting blood glucose level, and reducing the serum triglycerides (TG) and total cholesterol (TC). Histopathological examinations indicated MELNs diminished inflammatory infiltration of hepatocytes and amplified the area of islet B cells. In addition, MELNs decreased the oxidative stress levels in liver tissue and had good biocompatibility. In vitro experiments verified that MELNs improved the viability of glucosamine (GlcN) induced insulin-resistant hepatocytes. Furthermore, this study also revealed that MELNs upregulated GLUT4 & Nrf2 and down-regulated GSK-3ß via activating the PI3K/Akt signaling pathway, promoting the production of antioxidant enzymes, such as HO-1 and SOD, to reduce oxidative stress. CONCLUSION: MELNs mitigated the progression of type 2 diabetes in HFD/STZ mouse model. The underlying molecular mechanism is related to PI3K/Akt/GLUT4/GSK-3ß signaling pathway.

Anatomical distance affects functional connectivity at rest in medicine-free obsessive-compulsive disorder.

BACKGROUND: Brain functional abnormalities at rest have been observed in obsessive-compulsive disorder (OCD). However, whether and how anatomical distance influences functional connectivity (FC) at rest is ambiguous in OCD. METHODS: Using resting-state functional magnetic resonance imaging data, we calculated the FC of each voxel in the whole-brain and divided FC into short- and long-range FCs in 40 medicine-free patients with OCD and 40 healthy controls (HCs). A support vector machine (SVM) was used to determine whether the altered short- and long-range FCs could be utilized to distinguish OCD from HCs. RESULTS: Patients had lower short-range positive FC (spFC) and long-range positive FC (lpFC) in the left precentral/postcentral gyrus (t = -5.57 and -5.43; P < 0.05, GRF corrected) and higher lpFC in the right thalamus/caudate, left thalamus, left inferior parietal lobule (IPL) and left cerebellum CrusI/VI (t = 4.59, 4.61, 4.41, and 5.93; P < 0.05, GRF corrected). Furthermore, lower spFC in the left precentral/postcentral gyrus might be used to distinguish OCD from HCs with an accuracy of 80.77%, a specificity of 81.58%, and a sensitivity of 80.00%. CONCLUSION: These findings highlight that anatomical distance has an effect on the whole-brain FC patterns at rest in OCD. Meanwhile, lower spFC in the left precentral/postcentral gyrus might be applied in distinguishing OCD from HCs.

Tumor-suppressive miR-323a inhibits pancreatic cancer cell proliferation and glycolysis through targeting HK-2.

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 85% of all malignant pancreatic exocrine tumors and is one of the main causes of cancer-related fatalities. PDAC is characterized by a high glycolytic rate to ensure its survival as a result of hypovascularization and the desmoplastic reaction. In this study, microRNA 323a (miR-323a) was shown to be downregulated within pancreatic cancer tissues and cells, and enriched in the glucose metabolism pathway. In vitro, overexpression of miR-323a suppressed cell viability, DNA synthesis, and colony formation; in vivo, miR-323a overexpression suppressed the tumor growth within a xenograft mouse model. Regarding cellular glycolysis, miR-323a overexpression decreased glucose-6-phosphate levels, inhibited glucose uptake, and reduced lactate and adenosine triphosphate production. miR-323a was found to directly target hexokinase 2 (HK-2) and negatively regulated HK-2 expression. HK-2 overexpression exerted oncogenic effects on pancreatic cancer cells and promoted cellular glycolysis; more importantly, HK-2 overexpression partially eliminated the effects of miR-323a overexpression. In conclusion, miR-323a is downregulated within pancreatic cancer and serves as a tumor-suppressive miRNA through inhibiting cancer cell proliferation and glycolysis. miR-323a exerts its tumor-suppressive effects through targeting HK-2.

A simple and fast LC-MS/MS method for the simultaneous determination of tenofovir alafenamide and tenofovir in human plasma.

A simple and fast liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of tenofovir alafenamide (TAF) and tenofovir (TNF) in human plasma. A simple protein precipitation procedure was employed to extract analytes from plasma. Chromatographic separation was performed on an Eclipse Plus C18 column utilizing a fast gradient elution starting with 2% of 2 mM ammonium acetate-formic acid (100/0.1, v/v) followed by increasing the percentage of acetonitrile. Detection was performed on a tandem mass spectrometer equipped with an electrospray ionization source operated in the positive ionization mode, using the transitions m/z 477.2 → m/z 346.1 for TAF and m/z 288.1 → m/z 176.1 for TNF. TAF-d5 and TNF-d7 were used as the internal standard of TAF and TNF, respectively. The method was validated in the concentration ranges 1.25-500 ng/mlfor TAF and 0.300-15.0 ng/ml for TNF with acceptable accuracy and precision.

Decreased Nucleus Accumbens Connectivity at Rest in Medication-Free Patients with Obsessive-Compulsive Disorder.

Background: Patients with obsessive-compulsive disorder (OCD) experience deficiencies in reward processing. The investigation of the reward circuit and its essential connectivity may further clarify the pathogenesis of OCD. Methods: The current research was designed to analyze the nucleus accumbens (NAc) functional connectivity at rest in medicine-free patients with OCD. Forty medication-free patients and 38 gender-, education-, and age-matched healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. Seed-based functional connectivity (FC) was used to analyze the data. LIBSVM (library for support vector machines) was designed to identify whether altered FC could be applied to differentiate OCD. Results: Patients with OCD showed remarkably decreased FC values between the left NAc and the bilateral orbitofrontal cortex (OFC) and bilateral medial prefrontal cortex (MPFC) and between the right NAc and the left OFC at rest in the reward circuit. Moreover, decreased left NAc-bilateral MPFC connectivity can be deemed as a potential biomarker to differentiate OCD from HCs with a sensitivity of 80.00% and a specificity of 76.32%. Conclusion: The current results emphasize the importance of the reward circuit in the pathogenesis of OCD.

Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder.

Background: Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear. Methods: A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier. Results: Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%. Conclusion: Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.

Antidepressant effects of total iridoids of Valeriana jatamansi via the intestinal flora-blood-brain barrier pathway.

CONTEXT: Valeriana jatamansi Jones [syn. V. wallichii DC, (Valerianaceae)] (VJJ) is used to treat depression. OBJECTIVE: To explore the effects of total iridoids of VJJ extract (TIV) on chronic unpredictable mild stress (CUMS) in mice. MATERIALS AND METHODS: VJJ roots and rhizomes were extracted with 70% ethanol. CUMS rats were treated daily with fluoxetine (2.6 mg/kg, i.g.) or TIV (5.7, 11.4, and 22.8 mg/kg, i.g.) for 14 days. Male Kun Ming mice on normal chow and 0.5% CMC-Na solution were used as a control. Behavioural tests included the tail suspension (TST) and sucrose preference tests (SPT). Evans blue staining was used to evaluate blood-brain barrier (BBB) permeability. Western blotting was used to measure zonula occludens-1 (ZO-1) and occludin expression. 16S rRNA sequencing was used to analyse intestinal flora abundance. Tax4Fun was used to predict KEGG metabolic pathways. RESULTS: TIV treatment reduced TST time (117.35 ± 8.23 or 108.95 ± 6.76 vs. 144.45 ± 10.30 s), increased SPT (55.83 ± 7.24 or 53.12 ± 13.85 vs. 38.98 ± 5.43%), increased the abundance of phylum Firmicutes (86.99 ± 0.03 vs. 60.88 ± 0.19%) and genus Lactobacillus (75.20 ± 0.19 vs. 62.10 ± 0.13%), reduced the abundance of phylum Bacteroidetes (6.69 ± 0.06 or 11.50 ± 0.09 vs. 25.07 ± 0.20%). TIV increased carbohydrate metabolism (14.50 ± 3.00 × 10-3 or 14.60 ± 2.00 × 10-3 or 14.90 ± 2.00 × 10-3 vs.13.80 ± 4.00 × 10-3%), replication and repair functions (5.60 ± 1.00 × 10-3 or 5.60 ± 1.00 × 10-3 vs. 5.10 ± 4.00 × 10-3%), reduced the frequency of infectious disease (1.60 ± 2.00 × 10-4 or 1.90 ± 5.00 × 10-4 or 1.80 ± 3.00 × 10-4 vs. 2.20 ± 7.00 × 10-3%), BBB permeability (0.77 ± 0.30 vs. 1.81 ± 0.33 µg/g), and up-regulated the expression of ZO-1 (1.42-fold, 1.60-fold, 1.71-fold) and occludin (1.79-fold, 2.20-fold). CONCLUSIONS: TIV may modulate the intestinal flora, thereby inducing the expression of ZO-1 and occludin, protecting the BBB and exerting an antidepressant effect.

Increased cerebellar-default-mode network connectivity at rest in obsessive-compulsive disorder.

Abnormalities of the cerebellum and default-mode network (DMN) in patients with obsessive-compulsive disorder (OCD) have been widely reported. However, alterations of reciprocal functional connections between the cerebellum and DMN at rest in OCD remain unclear. Forty patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity (FC) and support vector machine (SVM) were applied to analyze the imaging data. Compared with HCs, patients with OCD exhibited increased FCs between the left Crus I-left superior medial prefrontal cortex (MPFC) and between the right Crus I-left superior MPFC, left middle MPFC, and left middle temporal gyrus (MTG). A significantly negative correlation was observed between the right Crus I-left MTG connectivity and the Yale-Brown Obsessive-Compulsive Scale compulsion subscale scores in the OCD group (r = - 0.476, p = 0.002, Bonferroni corrected). SVM classification analysis indicated that a combination of the left Crus I-left superior MPFC connectivity and the right Crus I-left middle MPFC connectivity can be used to discriminate patients with OCD from HCs with a sensitivity of 85.00%, specificity of 68.42%, and accuracy of 76.92%. Our study highlights the contribution of the cerebellar-DMN connectivity in OCD pathophysiology and provides new findings to OCD research.

The Association between Polymorphism of CARD8 rs2043211 and Susceptibility to Arteriosclerosis Obliterans in Chinese Han Male Population.

BACKGROUND AND AIMS: Cholesterol crystals have been shown to cause inflammation. As a response to cholesterol crystal accumulation, the NLRP3 inflammasome is activated to produce IL-1ß which eventually leads to atherosclerotic lesions. As a part of innate immunity, CARD8 is involved in the modulation of above mentioned inflammatory activities. The primary objective of this study was to investigate the association between polymorphism of CARD8 rs2043211 and susceptibility to arteriosclerosis obliterans (ASO) in Chinese Han male population. METHODS: 758 male arteriosclerosis obliterans patients and 793 male controls were genotyped for rs2043211 with the TaqMan allele assays. Fasting blood-glucose (FBG), total cholesterol (TC), triglycerides (TG), urea nitrogen, creatinine, Serum uric acid, high density lipoprotein, low density lipoprotein, ALT, AST, and IL-1ß in the blood were detected for all subjects. Clinical data were recorded to analyze the genotype-phenotype. Independent samples t-test was used to perform the comparisons between two groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to measure the strength of relationship in the genotype distribution and allele frequencies between patients and controls. The analysis of variance was used for a genotype-phenotype analysis of the ASO patients. RESULTS: The genotypic and allelic frequencies in the ASO group were significantly different from that in the control group (P = 0.014 by genotype, P = 0.003 by allele). Those carrying the genotype TT had a higher risk for ASO than those carrying the genotype AA (OR = 1.494, 95%CI1.131-1.974, P = 0.005).The difference was also significant after the adjustment for the history of smoking, TC, LDL, fasting blood glucose, systolic blood pressure and BMI(OR = 1.525, 95%CI1.158-2.009, P = 0.003). CONCLUSION: Our finding suggests that the polymorphism of CARD8 rs2043211 is probably associated with the development of ASO in Chinese Han male population.

Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome.

Recent research demonstrates that the choline-derived metabolite trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis and cardiovascular risks. The NLRP3 inflammasome responds to exogenous and endogenous danger signals involved in the development of atherosclerosis. Moreover, thioredoxin-interactive protein (TXNIP) activation is a key event linked to NLRP3 inflammasome via reactive oxygen species (ROS). Whether TMAO prime NLRP3 inflammasome via ROS-TXNIP pathway remains unclear. This study observed the expression of TXNIP-NLRP3 inflammasome stimulated by TMAO in human umbilical vein endothelial cells (HUVECs), aiming to elucidate the mechanism by which the TMAO may contribute to inflammation and endothelial dysfunction. Our data showed that TMAO significantly triggered oxidative stress and activated TXNIP-NLRP3 inflammasome whereat inflammatory cytokines interleukin (IL)-1ß and IL-18 were released in a dose- and time-dependent manner, but endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were inhibited. Moreover, TMAO-mediated effects were observably reversed by ROS inhibitor N-acetylcysteine (NAC) treatment or siRNA-mediated knockdown TXPIN and NLRP3. Taken together, our results firstly reveal that TMAO induces inflammation and endothelial dysfunction via activating ROS-TXNIP-NLRP3 inflammasome, suggest a likely mechanism for TMAO-dependent enhancement in atherosclerosis and cardiovascular risks.

Effect of Huperzine A on Aß-induced p65 of astrocyte in vitro.

Alzheimer's disease (AD) is the most common cause of dementia. Its pathology often accompanies inflammatory action, and astrocytes play important roles in such procedure. Rela(p65) is one of significant message factors in NF-κB pathway which has been reported high expression in astrocyte treated by Aß. HupA, an alkaloid isolated from Chinese herb Huperzia serrata, has been widely used to treat AD and observations reflected that it improves memory and cognitive capacity of AD patients. To reveal its molecular mechanisms on p65, we cultured astrocytes, built Aß-induced AD model, treated astrocytes with HupA at different concentrations, assayed cell viability with MTT, and detected p65 expression by immunohistochemistry and PCR. Our results revealed that treatment with 10 µM Aß1-42 for 24 h induced a significant increase of NF-κB in astrocytes; HupA significantly down-regulated p65 expression induced by Aß in astrocytes. This study infers that HupA can regulate NF-κB pathway to treat AD.

Altered resting-state functional organization within the central executive network in obsessive-compulsive disorder.

AIM: Obsessive-compulsive disorder (OCD) is associated with deficits in response inhibition and planning, which are governed by the central executive network. The objective of this study was to investigate both intra- and inter-regional resting-state connectivity within the central executive network in OCD. METHODS: Thirty OCD patients and 30 matched healthy controls were scanned using resting-state functional magnetic resonance imaging. The independent component analysis was used on a separate sample of healthy controls to generate the central executive network mask for the subsequent OCD analyses. Regional homogeneity (ReHo) and seed-based functional connectivity analyses were used to explore the differences between intra- and inter-regional synchronized activity within the central executive network in OCD patients at rest. RESULTS: Increased ReHo and functional connectivity in the key regions of the central executive network, such as the orbitofrontal cortex, dorsolateral prefrontal cortex, and the angular gyrus, were found in OCD patients. Furthermore, changes in both the ReHo within the orbitofrontal cortex and the functional connectivity between the orbitofrontal cortex and angular gyrus were negatively correlated with OCD duration. CONCLUSION: The increased resting-state functional organization within the central executive network may be related to OCD patients' deficits in cognitive control and symptom progression.

Supervised methods for symptom name recognition in free-text clinical records of traditional Chinese medicine: an empirical study.

Clinical records of traditional Chinese medicine (TCM) are documented by TCM doctors during their routine diagnostic work. These records contain abundant knowledge and reflect the clinical experience of TCM doctors. In recent years, with the modernization of TCM clinical practice, these clinical records have begun to be digitized. Data mining (DM) and machine learning (ML) methods provide an opportunity for researchers to discover TCM regularities buried in the large volume of clinical records. There has been some work on this problem. Existing methods have been validated on a limited amount of manually well-structured data. However, the contents of most fields in the clinical records are unstructured. As a result, the previous methods verified on the well-structured data will not work effectively on the free-text clinical records (FCRs), and the FCRs are, consequently, required to be structured in advance. Manually structuring the large volume of TCM FCRs is time-consuming and labor-intensive, but the development of automatic methods for the structuring task is at an early stage. Therefore, in this paper, symptom name recognition (SNR) in the chief complaints, which is one of the important tasks to structure the FCRs of TCM, is carefully studied. The SNR task is reasonably treated as a sequence labeling problem, and several fundamental and practical problems in the SNR task are studied, such as how to adapt a general sequence labeling strategy for the SNR task according to the domain-specific characteristics of the chief complaints and which sequence classifier is more appropriate to solve the SNR task. To answer these questions, a series of elaborate experiments were performed, and the results are explained in detail.

SARS-CoV-2 vaccines in China could reduce COVID-19-related respiratory syndromes and deaths: A retrospective cohort study.

Background: Information is limited regarding the effectiveness of the inactivated vaccine for COVID-19 approved in China in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when administered in real-world conditions. Methods: We retrospectively surveyed 1352 patients with a positive SARS-CoV-2 nucleic acid test treated at a major tertiary medical center in Foshan city (Guangdong, China) between November 2022 and February 2023. The exposure group was patients who had previously received the COVID-19 vaccine, which included patients who had received different doses of the vaccine and different vaccine types. The primary outcome of this study was the effectiveness of the vaccine in preventing severe disease and death among SARS-CoV-2-infected patients. Results: We found a mortality rate of 12.1 % associated with COVID-19. The results showed that an increase in the number of vaccine doses was associated with a reduction in in-hospital mortality. When compared to unvaccinated patients, vaccinated patients had an 8.5 % lower mortality rate. There was also a statistically significant reduction in the risk of death among vaccinated patients compared to unvaccinated patients (OR = 0.521 [95 % CI, 0.366 to 0.741]). Patients who had received the vaccine had a 22.8 % reduction in the risk of severe disease. In addition, the use of antiviral drugs decreased progressively with increasing vaccine doses (P < 0.05). Of these, anticoagulation, Paxlovid, and mechanical ventilation were used least frequently in the one-dose group. Conclusions: The vaccines approved in China mitigated the incidence of severe COVID-19 and reduced mortality. These findings suggest that COVID-19 vaccination can help to control the pandemic.

Application of phosphogypsum and phosphate-solubilizing fungi to Pb remediation: From simulation to in vivo incubation.

Phosphogypsum (PG) is the produced solid waste during phosphorus (P) extraction from phosphate rocks. PG is featured by its abundant PO43- and SO42-. This study investigated the utilization of PG as a material for lead (Pb) remediation, with the assistance of functional fungus. Aspergillus niger (A. niger) is a typical phosphate-solubilizing fungi (PSF), which has high ability to secret organic acids. Oxalic acid is its major secreted organic acid, which is often applied to enhance the P release from phosphate minerals. In this study, synthetic oxalic acid increased the immobilization rate of Pb2+ up to >99 % with the addition of PG. Then, it was observed that biogenic oxalic acid from A. niger can achieve comparable remediation effects. This was due to that PG could provide sufficient P for fungal growth, which allowed sustainable remediation. Subsequently, oxalic acid secreted by A. niger significantly increased the release of active P from PG, and then induced the formation of PPb minerals. In addition, other metabolites of A. niger (such as tyrosine-like substance) can also be complexed with Pb2+. Simultaneously, A. niger did not induce evidently elevation water-soluble fluorine (F) as PG contained abundant Ca2+. Moreover, this study elucidated that oversupply of PG promoted the formation of anglesite (Ksp = 1.6 × 10-8, relatively unstable), whereas the formation of lead oxalate (Ksp = 4.8 × 10-10, relatively stable) was reduced. This study hence shed a bright light on the sustainable utilization of PG for fungus-assisted remediation of heavy metals.

Effects of temperature-related changes on charred bone in soil: From P release to microbial community.

Phosphorus (P) is one of the most common limited nutrients in terrestrial ecosystems. Animal bones, with abundant bioapatite, are considerable P sources in terrestrial ecosystems. Heating significantly promotes P release from bone bioapatite, which may alleviate P limitation in soil. This study aimed to explore P release from charred bone (CB) under heating at various temperatures (based on common natural heating). It showed that heating at ∼300 °C significantly increased the P release (up to ∼30 mg/kg) from CB compared with other heating temperatures. Then, the subsequent changes of available P and pH induced evident alternation of soil microbial community composition. For instance, CB heated at ∼300 °C caused elevation of phosphate-solubilizing fungi (PSF) abundance. This further stimulated P mobility in the soil. Meanwhile, the fungal community assembly process was shifted from stochastic to deterministic, whereas the bacterial community was relatively stable. This indicated that the bacterial community showed fewer sensitive responses to the CB addition. This study hence elucidated the significant contribution of heated bone materials on P supply. Moreover, functional fungi might assist CB treated by natural heating (e.g., fire) to construct P "Hot Spots".

Pore evolution mechanisms during directed energy deposition additive manufacturing.

Porosity in directed energy deposition (DED) deteriorates mechanical performances of components, limiting safety-critical applications. However, how pores arise and evolve in DED remains unclear. Here, we reveal pore evolution mechanisms during DED using in situ X-ray imaging and multi-physics modelling. We quantify five mechanisms contributing to pore formation, migration, pushing, growth, removal and entrapment: (i) bubbles from gas atomised powder enter the melt pool, and then migrate circularly or laterally; (ii) small bubbles can escape from the pool surface, or coalesce into larger bubbles, or be entrapped by solidification fronts; (iii) larger coalesced bubbles can remain in the pool for long periods, pushed by the solid/liquid interface; (iv) Marangoni surface shear flow overcomes buoyancy, keeping larger bubbles from popping out; and (v) once large bubbles reach critical sizes they escape from the pool surface or are trapped in DED tracks. These mechanisms can guide the development of pore minimisation strategies.