Downregulation of WNK4 expression facilitates the proliferation of gastric cancer cells via activation of the STAT3 signaling pathway.

WNK lysine deficient protein kinase 4 (WNK4) has been shown to be significantly associated with cancer progression. Nevertheless, its involvement in gastric cancer (GC) is unclear. The objective of this work was to investigate the WNK4's regulatory mechanism in GC. Quantitative RT-PCR and immunoblots revealed that WNK4 expression was downregulated in GC and that low expression of WNK4 was strongly linked to poor prognosis. Functional assays including cell counting kit-8 assay and colony formation assay demonstrated that overexpression of WNK4 led to limited tumor proliferation both in vitro and in vivo, while the WNK4 reduction yielded to the opposite results. Gene Set Enrichment Analysis (GSEA) indicated a potential association between WNK4 and the signal transducer and activator of transcription (STAT3). WNK4 suppressed the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in GC cells. The inhibition of the STAT3 pathway with Stattic reversed growth and proliferation induced by WNK4 knockdown in GC cells. These findings provide new insights for identifying key therapeutic targets for GC in the future.

A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy.

Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.

Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway.

Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh-7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec-1, CQ, and Z-VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin-1, and liproxstatin-1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe2+ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin-treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth.

Glucocorticoid activates STAT3 and NF-κB synergistically with inflammatory cytokines to enhance the anti-inflammatory factor TSG6 expression in mesenchymal stem/stromal cells.

Glucocorticoid (GC) is essential for maintaining immune homeostasis. While GC is known to regulate the expression of genes related to inflammation in immune cells, the effects of GC, especially in the presence of inflammation, on non-immune cells remain largely unexplored. In particular, the impact of GC on inflammatory cytokine-induced immune modulatory responses of tissue stromal cells is unknown, though it has been widely used to modulate tissue injuries. Here we found that GC could enhance the expression of TSG6, a vital tissue repair effector molecule, in IFNγ and TNFα treated human umbilical cord (UC)-MSCs. NF-κB activation was found to be required for GC-augmented TSG6 upregulation. STAT3, but not STAT1, was also found to be required for the TSG6 upregulation in MSCs exposed to IFNγ, TNFα and GC. Moreover, the phosphorylation (activation) of STAT3 was attenuated when NF-κB was knocked down. Importantly, human UC-MSCs pretreated with a cocktail containing GC, IFNγ, and TNFα could significantly enhance the therapeutic effect of human UC-MSCs in an acute lung injury mouse model, as reflected by reduced infiltration of immune cells and down-regulation of iNOS in macrophages in the lung. Together, the findings reveal a novel link between GR, NF-κB and STAT3 in regulating the immunomodulatory and regenerative properties of MSCs, providing novel information for the understanding and treatment of inflammatory conditions.

3D-3D dentition superimposition for individual identification: A study of an Eastern Chinese population.

Recently, 3D dental intraoral scanning technology has been developed rapidly and applied widely in everyday dental practice. Since 3D dental scanning could provide valuable personal information, it enabled researchers to develop novel procedures for individual identification through 3D-3D dentition superimposition. This study aimed to test the applicability of this method in an Eastern Chinese population and propose a threshold for personal identification. For this purpose, 40 volunteers were recruited, and the initial 80 (upper and lower) 3D intraoral scans (IOS) were collected. After one year, 80 IOS of these volunteers were repeatedly collected. In addition, the other 120 IOS of 60 patients were extracted from the database. The 3D models were trimmed, aligned, and superimposed via Geomagic Control X software, and then the root mean square (RMS) value of point-to-point distance between the two models was calculated. The superimposition of two IOS belonging to the same individual was considered as a match, and superimposition of two IOS belonging to different individuals was considered as a mismatch. Totally, superimpositions of 80 matches and 3120 mismatches were obtained. Intra- and inter-observer errors were assessed through the calculation of relative technical error of measurement (rTEM). Mann-Whitney U test verified possible statistically significant differences between matches and mismatches (P < 0.05). The rTEM of intra- and inter-observer repeatability analyses was lower than 4.7 %. The range of RMS value was 0.05-0.18 mm in matches and 0.72-2.28 mm in mismatches without overlapping. The percentage of accurate identification reached 100 % in blind test through an arbitrary RMS threshold of 0.45 mm. The results indicated that individual identification through the 3D-3D dentition superimposition was effective in Eastern Chinese population. Successful identification could be achieved with high probability when the RMS value of the point-to-point distance of two dentitions is <0.45 mm.

Mesenchymal stem cells alleviate systemic sclerosis by inhibiting the recruitment of pathogenic macrophages.

Systemic sclerosis (SSc) is a recalcitrant autoimmune disease for which there is no cure. Mesenchymal stem cell (MSC)-based treatment has emerged as a promising therapeutic option for several autoimmune diseases. Previously, we found that the immunoregulatory potential of MSCs can be greatly enhanced by IFN-γ and TNF-α. Here, we found that IFN-γ- and TNF-α-pretreated MSCs significantly alleviated skin fibrosis in a bleomycin (BLM)-induced SSc model. Macrophages were found to be the predominant profibrotic immune cell population in the pathogenesis of SSc. The accumulation of macrophages was significantly decreased by MSC treatment. Importantly, MSCs primarily reduced the population of maturing macrophages with high CCR2 expression by inhibiting the generation of CCL2 from fibroblasts and macrophages. This finding may help to improve MSC-based clinical treatments for SSc patients.

Clinical Monitoring of Serum Levels of Vitamins A, D and E in Children with Recurrent Respiratory Tract Infections of Different Ages: A Clinical Controlled Trial.

Objective: To study serum levels of vitamins A, D and E in children with recurrent respiratory tract infections of different ages and the correlation. Methods: The clinical data of two groups of children of different ages were collected. The serum levels and deficiencies of vitamins A, D and E in children were statistically analyzed. Results: The proportions of premature infants, low body weight infants, special physique, hospitalization history, hypocalcemia, living in a bungalow, and daily outdoor activities in less than 30 minutes in the case group were higher than those in the control group (χ 2=4.507, 5.165, 7.040, 14.907, 4.267, 33.800, 4.507, 8.571, P < 0.05). The serum levels of vitamins A, D and E of children aged 0-1, 2-5, and 6-12 in the case group were lower than those in the control group (P < 0.05). Compared with the control group, the serum vitamin A level of children in the case group was lower (t = 2.631, P < 0.05), and the deficiency rate was higher (χ 2=24.200, P < 0.05). Conclusion: Serum levels of vitamins A, D and E, which are related to birth mode, physical fitness, hospitalization history, hypocalcemia, vitamin deficiency, living environment, and daily outdoor activity time, vary in children with recurrent respiratory tract infections of different ages, and are lower in children with recurrent respiratory tract infections than in healthy children.

Dynamic monitoring and a clinical correlation analysis of the serum vitamin A, D, and E levels in children with recurrent respiratory tract infections.

OBJECTIVE: To investigate the correlation of the serum vitamin A, D, and E (VA, VD, and VE) levels with the occurrence and development of recurrent respiratory tract infections (RRTIs). METHODS: A total of 129 children with respiratory tract infections (RTIs) treated in our hospital from January 2018 to February 2020 (the RTIs group) and 50 healthy children undergoing physical examinations (the control group) in our hospital were recruited as the study cohort. The serum VA, VD, and VE levels were measured upon admission (the active phase) and at two weeks after discharge (the stable phase). The serum VA, VD, and VE levels in the children with RRTIs were compared with the levels in the control group, and the correlation between these three vitamins and the occurrence and development of RRTIs was analyzed. RESULTS: The RRTIs group and the RTIs group witnessed markedly lower serum VA, VD, VE, and humoral immunity index levels, including IgG, IgA, and IgM, compared to the control group, with an apparent lower outcome in the RRTIs group than in the RTIs group. The serum levels of the above indexes in the RRTIs children were reduced in the active phase compared with the stable phase. A Pearson correlation analysis showed a positive correlation between VA and IgA. A multivariate logistic regression analysis revealed that a low BMI (Body mass index), prematurity, VA deficiency, VD deficiency, and VE deficiency were the risk factors for RRTIs in children, and outdoor activity was the protective factor. CONCLUSION: The VA, VD, and VE levels are closely related to RRTIs in children. It is important to determine and supplement the VA, VD, and VE levels to prevent RTIs in children.

AKT/foxo3a signal pathway mediates the protective mechanism of resveratrol on renal interstitial fibrosis and oxidative stress in rats with unilateral ureteral obstruction.

OBJECTIVE: To explore whether protein kinase B (serine/threonrine kinase, AKT)/forkhead box protein O3a (foxo3a) pathway mediates the protective mechanism of resveratrol (RSV) on renal interstitial fibrosis (RIF) and oxidative stress. METHODS: Sprague-Dawley (SD) rats were grouped into Sham group, unilateral ureteral obstruction (UUO) group and UUO + RSV group. HE staining was used to test the pathological damage of RIF intervened by RSV, biochemical analyzer was used to measure serum renal injury indexes (creatinine, Cr, blood urea nitrogen, Bun), and enzyme-linked immunosorbent assay (ELISA) was used to detect oxidative stress indexes (malondialdehyde, MDA; glutathione, GSH; superoxide dismutase, SOD). AKT/FoxO3a signaling pathway markers and renal interstitial indexes were measured by western blot analysis. RESULTS: Compared with Sham group, HE staining in UUO group showed significant RIF pathological damage; Cr and Bun indexes were increased, and AKT/FoxO3a signal pathway was activated, as indicated by increased p-AKT/AKT and p-FoxO3a/FoxO3a; TGF-ß1 and α-SMA protein levels in fibrosis indexes were increased, while E-cadherin decreased; MDA was increased, GSH and SOD were decreased in oxidative stress indexes, while those in UUO + RSV group were improved. CONCLUSION: AKT/foxo3a signaling pathway mediates the protective mechanism of RSV on RIF and oxidative stress in UUO rats, and RSV can improve RIF and oxidative stress in UUO rats by inhibiting AKT/foxo3a signaling pathway.

Soybean diacylglycerol regulates lipid metabolism in D-galactose-induced aging rats by altering gut microbiota and gene expression of colonic epithelial cells.

Lipid metabolism is closely related to the health of aging bodies and its disorder often leads to cardiovascular diseases and chronic diseases. Dietary fat is one of the important sources of body fat, which affects the body's lipid metabolism. However, how dietary fat affects lipid metabolism in aging bodies has not been reported. Thus, the effects of soybean diacylglycerol (DAG) on lipid metabolism in D-galactose-induced aging rats were investigated by detecting the serum biochemical indexes, hepatocyte morphology, gut microbiota changes, and gene expression of colonic epithelial cells. The results showed that DAG alleviated the lipid metabolism disorders, and the hepatocyte morphology of aging rats fed DAG was normal. 16S rDNA analysis showed that DAG restored Eisenbergiella and Veillonella that were missing in aging rats. The relative abundances of Romboutsia and Ruminococcus_2 decreased and the relative abundance of Lachnospiraceae NK4A136 group increased significantly with the influence of DAG (P < 0.05). Gene expression profiles showed that the gene expression of colon epithelial cells was altered by DAG and DAG downregulated the genes Lipe and Fabp4 related to the lipolysis of adipocytes. In conclusion, DAG regulated the lipid metabolism of aging rats by regulating gut microbiota and gene expression of colonic epithelial cells.

Metabolomic analysis and oxidative stress response reveals the toxicity in Escherichia coli induced by organophosphate flame retardants tris(2-chloroethyl) phosphate and triphenyl phosphate.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that are increasingly being used in consumer commodities. The adverse effects on biota induced by tris(2-chloroethyl) phosphate (TCEP) and triphenyl phosphate (TPHP) have become a growing concern. Unfortunately, toxic mechanisms at the molecular level for OPFRs in organisms are still lacking. Herein, Escherichia coli (E.coli) was exposed to TCEP and TPHP for 24 and 48 h to reveal oxidative stress response and molecular toxicity mechanisms. The results indicated that promotion of ROS overload occurred at higher dosages groups. The levels of SOD and CAT were significantly elevated along with the increase of MDA attributed to lipid peroxidation. Additionally, apoptosis rates increased, accompanied by a decline in membrane potential and Na+/K+-ATPase and Ca2+/Mg2+-ATPase contents, signifying that E. coli cytotoxicity induced by TCEP and TPHP was mediated by oxidative stress. Based on metabolomic analysis, different metabolic pathways were disrupted, including glycolysis/gluconeogenesis, pentose phosphate metabolism, purine metabolism, glutathione metabolism, amino acid biosynthesis, butanoate metabolism, alanine and aspartate metabolism. Most differentially expressed metabolites were downregulated, indicating an inhibitory effect on metabolic functions and key metabolic pathways. These findings generated new insights into the potential environmental risks of OPFRs in aquatic organisms.

Treatment of facial and non-facial lentigines with a 730 nm picosecond titanium: Sapphire laser is safe and effective.

OBJECTIVE: A 730 nm picosecond-domain laser was developed to improve the clearance of pigmented lesion and reduce adverse events. This study assessed the safety and efficacy of this system for the clearance of lentigines and explores how the short picosecond pulses interact with tissue via histology. STUDY DESIGN AND METHODS: Twenty subjects with Fitzpatrick skin types II-IV were enrolled in this prospective, IRB-approved study. Four treatments were administered using a 730 nm picosecond-domain laser. Pre- and posttreatment photos were assessed by blinded reviewers at 4- and 12-week follow-up visits, using a 5-point clearance scale. Subject satisfaction was measured using a 5-point scale. Investigator Global Improvement Score (IGIS) was performed at the 4- and 12-week follow-up visits, using an 11-point clearance scale. Subject pain level was measured using an 11-point scale (no pain [0], extreme pain [10]). Histology of 730 and 532 nm picosecond pulses was compared with 755 and 532 nm nanosecond pulses. RESULTS: Sixteen subjects with a total of 118 discontinuous treatment areas, each comprised of 1-20 lesions, completed all study visits. Thirty body regions were studied, including arms (6), hands (16), scalp (1), forehead (2), face (3), and back (2). Spot sizes ranging from 2 to 5 mm diameters were used with fluences ranging from 0.8 to 4.0 J/cm2 . Mean pain score was 3.6 of 10 for all four treatments. Ninety-nine percent of randomly paired 4-week posttreatment images and 100% of 12-week posttreatment images were correctly identified from their respective baseline images by three blinded reviewers. Mean IGIS demonstrated scores of 6.7 and 7.0 at 4- and 12-week follow-up visits, respectively. At the 4- and 12-week follow-up visits, 76% and 73% of subjects, respectively, were satisfied to highly satisfied. The mean clearance score for all 118 treatment areas was 3 of 4 in follow-up visits. At 12-week follow-up, 36% of 118 treatment areas had a clearance score of 4, and 38% had a clearance score of 3. Post treatment, there was typical erythema, edema, dryness, crusting, and itching but negligible purpura, no pinpoint bleeding, blistering or scarring, and no significant hyperpigmentation or hypopigmentation. Histology showed diffuse, focal epidermal vacuolization ~5-10 µm in diameter and mild extravasation of erythrocytes with 730 nm picosecond pulses, while diffuse epidermal vacuolization was observed with coalescence of vacuoles (~20-100 µm), junctional clefting and mild extravasation of erythrocytes with 755 nm nanosecond pulses. Picosecond pulses of the wavelength of 532 nm produced diffuse, focal epidermal vacuolization and larger dermal vacuoles to depths of 500 µm, while 532 nm nanosecond pulses produced diffuse epidermal vacuolization with coalescence of vacuoles and marked dermal hemorrhage. CONCLUSION: This study demonstrated the potential of a new 730 nm picosecond-domain laser for the clearance of lentigines. The results showed good clearance with no adverse events and good subject satisfaction in patients with skin type II-III. Additional studies need to be conducted on darker skin types. The histopathologic findings demonstrate that the picosecond 730 nm laser produces excellent selectivity for pigment with minimal disruption of the dermal-epidermal junction and may therefore reduce healing times and the risk of adverse events.

Initial respiratory support modality and outcome in preterm infants with less than 32 weeks of gestation in China: A multicentre retrospective cohort study.

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma.

Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C-indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.

pH-dependent biological sulfidogenic processes for metal-laden wastewater treatment: Sulfate reduction or sulfur reduction?

Both biological sulfate reduction process and sulfur reduction process are attractive technologies for metal-laden wastewater treatment. However, the acidity stress of metal-laden wastewater could affect the sulfidogenic performance and the microbial community, weaken the stability, efficiency and cost-effectiveness of the biological sulfidogenic processes (BSP). In this study, long-term lab-scale trials were conducted with a sulfate-reducing bioreactor and a sulfur-reducing bioreactor to evaluate the effects of acidity on sulfidogenic activities and the microbial community of the BSP. In the 300-day trial, the sulfate-reducing bacteria (SRB)-driven BSP was stable in terms of sulfidogenic performance and microbial community with the decline of pH, while the sulfur-reducing bacteria (S0RB)-driven BSP achieved high-rate and low-cost sulfide production under neutral conditions but unstable under acidic conditions. With the decline of pH, the sulfide production rate (SPR) of the SRB-driven BSP stably increased from 30 to 83 mg S/L-h; while it decreased from 56 to 37 mg S/L-h in the S0RB-driven BSP with high fluctuation. The results of estimation were consistent with the thermodynamical calculations, in which the sulfur reduction process showed a better performance at pH 5-7, while the sulfate reduction process might gain more energy when pH<5. The stable sulfidogenic performance and microbial community diversity of the SRB-driven BSP could be attributed to the alkalinity produced in sulfate reduction to buffer the acidic stress. In comparison, the microbial community in the S0RB-driven BSP was significantly re-shaped by acidity stress, and the predominant sulfidogenic bacterium changed from Desulfovibrio at neutral condition, to Desulfurella at pH≤5.4. The stability of the microbial community significantly affected the SPR and the operational cost. Nevertheless, the organic consumption for sulfide production of the S0RB-driven BSP was still less than the SRB-driven BSP even in acidic conditions. Collectively, the S0RB-driven BSP was recommended under neutral or mild acid conditions, while the SRB-driven BSP was more suitable under fluctuating pH conditions, especially at low pH. Overall, this study presented the long-term performance of SRB- and S0RB-driven BSP under varying pH conditions, and provided guidance to determine the suitable BSP and operational cost for different metal-laden wastewater.

Cytoplasmic and nuclear genome variations of rice hybrids and their parents inform the trajectory and strategy of hybrid rice breeding.

The male sterility (MS) line is a prerequisite for efficient production of hybrid seeds in rice, a self-pollinating species. MS line breeding is pivotal for hybrid rice improvement. Understanding the historical breeding trajectory will help to improve hybrid rice breeding strategies. Maternally inherited cytoplasm is an appropriate tool for phylogenetic reconstruction and pedigree tracing in rice hybrids. In this study, we analyzed the cytoplasmic genomes of 1495 elite hybrid rice varieties and identified five major types of cytoplasm, which correspond to different hybrid production systems. As the cytoplasm donors for hybrids, 461 MS lines were also divided into five major types based on cytoplasmic and nuclear genomic architecture. Specific core accessions cooperating with different fertility-associated genes drove the sequence divergence of MS lines. Dozens to hundreds of convergent and divergent selective sweeps spanning several agronomic trait-associated genes were identified among different types of MS lines. We further analyzed the cross patterns between different types of MS lines and their corresponding restorers. This study systematically analyzed the cytoplasmic genomes of rice hybrids revealed their relationships with nuclear genomes of MS lines, and illustrated the trajectory of hybrid rice breeding and the strategies for breeding different types of MS lines providing new insights for future improvement of hybrid rice.

Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019.

BACKGROUND: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. STUDY DESIGN: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. RESULTS: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045). CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

The correlation between the vitamin A, D, and E levels and recurrent respiratory tract infections in children of different ages.

OBJECTIVE: To investigate the correlation between the vitamin A, D, and E levels and recurrent respiratory tract infections (RRTIs) in children of different ages. METHODS: A total of 150 RRTI patients were divided into three groups: the 0 to 2 year-old group, the 3-5 year-old group, and the 6-14 year-old group. Collectively, we refer to the three groups as the RRTI group. The serum vitamin A, D and E levels were measured in the three groups. Healthy children without RRTIs were recruited as a control group. The correlations between the changes in the vitamin A, D, and E levels and the RRTIs were analyzed. RESULTS: The vitamin A, D, and E levels decreased significantly in the children with RRTIs, but only the vitamin A and D levels were negatively correlated with the incidence of RRTIs, while the vitamin E levels were not significantly correlated with the incidence of RRTIs. The follow-up results showed that the serum vitamin A, D, and E levels in the RRTI group were significantly increased after the treatment, and the WBC and CRP levels were remarkably reduced. CONCLUSION: Monitoring the serum vitamin A and D levels helps determine the disease severity, and the supplementation of adequate vitamin A and D through diet or drugs is of great help in treating RRTIs.

Elemental sulfur-driven sulfidogenic process under highly acidic conditions for sulfate-rich acid mine drainage treatment: Performance and microbial community analysis.

Elemental sulfur-driven sulfidogenic process has been demonstrated to be more economical and energy-efficient than sulfate-driven sulfidogenic process when treating metal-laden wastewater. In previous studies, we observed that the polysulfide-involved indirect sulfur reduction ensured the superiority of sulfur over sulfate as the electron acceptor in the sulfidogenic process under neutral or weak-alkaline conditions. However, realizing high-rate sulfur reduction process for acid mine drainage (AMD) treatment without pH amelioration is still a great challenge because polysulfide cannot exist under acidic conditions. In this study, a laboratory-scale sulfur-packed bed reactor was therefore continuously operated with a constant sulfate concentration (~1300 mg S/L) and decreasing pH from 7.3 to 2.1. After 400 days of operation, a stable sulfide production rate (38.2 ± 7.6 mg S/L) was achieved under highly acidic conditions (pH 2.6-3.5), which is significantly higher than those reported in sulfate reduction under similar conditions. In the presence of high sulfate content, elemental sulfur reduction could dominate over sulfate reduction under neutral and acidic conditions, especially when the pH ≥ 6.5 or ≤ 3.5. The decreasing pH significantly reduced the diversity of microbial community, but did not substantially influence the abundance of functional genes associated with organic and sulfur metabolisms. The predominant sulfur-reducing genera shifted from Desulfomicrobium under neutral conditions to Desulfurella under highly acidic conditions. The high-rate sulfur reduction under acidic conditions could be attributed to the combined results of high abundance of Desulfurella and low abundance of sulfate-reducing bacteria (SRB). Accordingly, sulfur reduction process can be developed to achieve efficient and economical treatment of AMD under highly acidic conditions (pH ≤ 3.5).