Evaluation of effects of heat released from SOC decomposition on soil carbon stock and temperature.

Heat released from soil organic carbon (SOC) decomposition (referred to as microbial heat hereafter) could alter the soil's thermal and hydrological conditions, subsequently modulate SOC decomposition and its feedback with climate. While understanding this feedback is crucial for shaping policy to achieve specific climate goal, it has not been comprehensively assessed. This study employs the ORCHIDEE-MICT model to investigate the effects of microbial heat, referred to as heating effect, focusing on their impacts on SOC accumulation, soil temperature and net primary productivity (NPP), as well as implication on land-climate feedback under two CO2 emissions scenarios (RCP2.6 and RCP8.5). The findings reveal that the microbial heat decreases soil carbon stock, predominantly in upper layers, and elevates soil temperatures, especially in deeper layers. This results in a marginal reduction in global SOC stocks due to accelerated SOC decomposition. Altered seasonal cycles of SOC decomposition and soil temperature are simulated, with the most significant temperature increase per unit of microbial heat (0.31 K J-1) occurring at around 273.15 K (median value of all grid cells where air temperature is around 273.15 K). The heating effect leads to the earlier loss of permafrost area under RCP8.5 and hinders its restoration under RCP2.6 after peak warming. Although elevated soil temperature under climate warming aligns with expectation, the anticipated accelerated SOC decomposition and large amplifying feedback on climate warming were not observed, mainly because of reduced modeled initial SOC stock and limited NPP with heating effect. These underscores the multifaceted impacts of microbial heat. Comprehensive understanding of these effects would be vital for devising effective climate change mitigation strategies in a warming world.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Changes in the gut microbiome of patients with esophageal cancer: a systematic review and meta-analysis based on 16S gene sequencing technology.

BACKGROUND: Esophageal cancer (EC) possesses a high degree of malignancy and exhibits poor therapeutic outcomes and prognosis. However, its pathogenesis remains unclear. With the development of macrogene sequencing technology, changes in the intestinal flora have been found to be highly related to the development of EC, although discrepancies and controversies remain in this research area. MATERIALS AND METHODS: We comprehensively searched the PubMed, EMBASE, and Cochrane's Central Controlled Trials Register and the Scientific Network's database search projects based on systematically reviewed preferred reporting projects and meta-analyses. We used Engauge Digitizer for data extraction and Stata 15.1 for data analysis. In addition, we used the Newcastle-Ottawa Scale for grade grading and forest and funnel plots, sensitivity, and Egger and Beggar tests to evaluate the risk of bias. RESULTS: This study included 10 studies that assessed stool, tumor, and nontumor esophageal mucosa (gastroscopy and surgical resection) samples from 527 individuals, including 273 patients with EC and 254 healthy control group. We observed remarkable differences in microbial diversity in EC patients compared to healthy controls. The Chao1 index (46.01 vs. 42.67) was significantly increased in EC patients, whereas the Shannon index (14.90 vs. 19.05), ACE (39.24 vs. 58.47), and OTUs(28.93 vs. 70.10) were significantly lower. At the phylum level, the abundance of Bacteroidetes (37.89 vs. 32.77) increased significantly, whereas that of Firmicutes (37.63 vs. 38.72) decreased significantly; the abundance of Clostridium and Verruciformis increased, while that of Actinobacteria and Proteobacteria decreased to varying degrees. The abundance of Bacteroides (8.60 vs. 15.10) and Streptococcaceae (15.08 vs. 27.05) significantly reduced in EC. CONCLUSIONS: According to our meta-analysis, in patients with EC, the Chao1 index increased, whereas the Shannon and the OTUs decreased. At the phylum level, the abundance of Firmicutes decreased significantly, whereas that of Bacteroidetes and Proteobacteria increased significantly. At the genus/family level, the abundance of Bacteroidaceae, Prevotellaceae and Streptococcaceae decreased significantly, whereas that of Veillonellaceae increased. This meta-analysis identified changes in gut microbiota in patients with EC; however, its conclusions were inconsistent.

The associations of maternal liver biomarkers in early pregnancy with the risk of gestational diabetes mellitus: a prospective cohort study and Mendelian randomization analysis.

Background: Associations of liver function with the risk of gestational diabetes mellitus (GDM) remain unclear. This study aimed to examine the relationship and the potential causality between maternal liver biomarkers and the risk of subsequent GDM, as well as to evaluate the interaction between liver biomarkers and lipids on GDM risk. Methods: In an ongoing Zhoushan Pregnant Women Cohort, pregnant women who finished the first prenatal follow-up record, underwent liver function tests in early pregnancy, and completed the GDM screening were included in this study. Logistic regression models were used to investigate the association, and the inverse-variance weighted method supplemented with other methods of two-sample Mendelian randomization (MR) analysis was applied to deduce the causality. Results: Among 9,148 pregnant women, 1,668 (18.2%) developed GDM. In general, the highest quartile of liver function index (LFI), including ALT, AST, GGT, ALP, and hepatic steatosis index, was significantly associated with an increased risk of GDM (OR ranging from 1.29 to 3.15), especially an elevated risk of abnormal postprandial blood glucose level. Moreover, the causal link between ALT and GDM was confirmed by the MR analysis (OR=1.28, 95%CI:1.05-1.54). A significant interaction between AST/ALT and TG on GDM risk was observed (P interaction = 0.026). Conclusion: Elevated levels of LFI in early pregnancy were remarkably associated with an increased risk of GDM in our prospective cohort. Besides, a positive causal link between ALT and GDM was suggested.

Genome-Wide Identification and Expression Analysis of the GRAS Gene Family and Their Responses to Heat Stress in Cymbidium goeringii.

The GRAS gene family, responsible for encoding transcription factors, serves pivotal functions in plant development, growth, and responses to stress. The exploration of the GRAS gene family within the Orchidaceae has been comparatively limited, despite its identification and functional description in various plant species. This study aimed to conduct a thorough examination of the GRAS gene family in Cymbidum goeringii, focusing on its physicochemical attributes, phylogenetic associations, gene structure, cis-acting elements, and expression profiles under heat stress. The results show that a total of 54 CgGRASs were pinpointed from the genome repository and categorized into ten subfamilies via phylogenetic associations. Assessment of gene sequence and structure disclosed the prevalent existence of the VHIID domain in most CgGRASs, with around 57.41% (31/54) CgGRASs lacking introns. The Ka/Ks ratios of all CgGRASs were below one, indicating purifying selection across all CgGRASs. Examination of cis-acting elements unveiled the presence of numerous elements linked to light response, plant hormone signaling, and stress responsiveness. Furthermore, CgGRAS5 contained the highest quantity of cis-acting elements linked to stress response. Experimental results from RT-qPCR demonstrated notable variations in the expression levels of eight CgGRASs after heat stress conditions, particularly within the LAS, HAM, and SCL4/7 subfamilies. In conclusion, this study revealed the expression pattern of CgGRASs under heat stress, providing reference for further exploration into the roles of CgGRAS transcription factors in stress adaptation.

20( S )-Protopanaxatriol Improves Atherosclerosis by Inhibiting Low-Density Lipoprotein Receptor Degradation in ApoE KO Mice.

ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.

Breastfeeding, Gestational Diabetes Mellitus, Size at Birth and Overweight/Obesity in Early Childhood.

Background: Breastfeeding appears to reduce the risk of childhood overweight/obesity. However, it remains unclear whether this protective effect persists among high-risk populations. This study aims to investigate the association of breastfeeding with the risk of overweight/obesity in early childhood and whether this association is altered by gestational diabetes mellitus (GDM) or size at birth. Methods: Feeding practices during the first 12 months of age and weight and length at 12-36 months of age were collected. Full breastfeeding includes exclusive and predominant breastfeeding. Children with body mass index (BMI) values greater than 1 standard deviation from the mean of sex- and age-specific BMI were classified as overweight/obese. Multiple generalized estimating equations models were applied to analyze the associations of full breastfeeding duration with overweight/obesity risk. Results: Among all participants (n = 9329), infants with a longer full-breastfeeding duration had a reduced risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Infants exposed to GDM and those born large for gestational age (LGA) had a higher risk of overweight/obesity in early childhood. Among infants of mothers with GDM (n = 1748), infants with full breastfeeding for greater than 6 months (aOR: 0.58; 95% CI: 0.44, 0.78) showed a decreased risk of overweight/obesity in early childhood compared with those breastfed for less than one month. Among LGA infants (n = 1279), infants with full breastfeeding for 3-5 months (aOR: 0.66; 95% CI: 0.57, 0.76) and greater than 6 months (aOR: 0.70; 95% CI: 0.56, 0.88) showed a decreased risk of overweight/obesity in early childhood. Similar results were observed among LGA infants of mothers with GDM. Conclusions: Initiating and prolonging breastfeeding would reduce the risk of overweight/obesity in early childhood, and LGA infants and infants born to mothers with GDM would experience greater benefits.

The Evolution of the WUSCHEL-Related Homeobox Gene Family in Dendrobium Species and Its Role in Sex Organ Development in D. chrysotoxum.

The WUSCHEL-related homeobox (WOX) transcription factor plays a vital role in stem cell maintenance and organ morphogenesis, which are essential processes for plant growth and development. Dendrobium chrysotoxum, D. huoshanense, and D. nobile are valued for their ornamental and medicinal properties. However, the specific functions of the WOX gene family in Dendrobium species are not well understood. In our study, a total of 30 WOX genes were present in the genomes of the three Dendrobium species (nine DchWOXs, 11 DhuWOXs, and ten DnoWOXs). These 30 WOXs were clustered into ancient clades, intermediate clades, and WUS/modern clades. All 30 WOXs contained a conserved homeodomain, and the conserved motifs and gene structures were similar among WOXs belonging to the same branch. D. chrysotoxum and D. huoshanense had one pair of fragment duplication genes and one pair of tandem duplication genes, respectively; D. nobile had two pairs of fragment duplication genes. The cis-acting regulatory elements (CREs) in the WOX promoter region were mainly enriched in the light response, stress response, and plant growth and development regulation. The expression pattern and RT-qPCR analysis revealed that the WOXs were involved in regulating the floral organ development of D. chrysotoxum. Among them, the high expression of DchWOX3 suggests that it might be involved in controlling lip development, whereas DchWOX5 might be involved in controlling ovary development. In conclusion, this work lays the groundwork for an in-depth investigation into the functions of WOX genes and their regulatory role in Dendrobium species' floral organ development.

Acidithiobacillus acidisediminis sp. nov., an acidophilic sulphur-oxidizing chemolithotroph isolated from acid mine drainage sediment.

Strain S30A2T, isolated from the acid mine drainage sediment of Mengzi Copper Mine, Yunnan, is proposed to represent a novel species of the sulphur-oxidizing genus Acidithiobacillus. Cells were Gram-stain-negative, non-endospore forming, highly motile with one or two monopolar flagella and rod-shaped. The strain was mesophilic, growing at 30-50 °C (optimum, 38 °C), acidophilic, growing at pH 2.0-4.5 (optimum, pH 2.5), and tolerant of 0-4 % (w/v; 684 mol l-1) NaCl. The 16S rRNA gene-based sequence analysis showed that strain S30A2T belongs to the genus Acidithiobacillus and shows the largest similarity of 96.6 % to the type strain Acidithiobacillus caldus KUT. The genomic DNA G+C content of strain S30A2T was 59.25 mol%. The average nucleotide identity ANIb and ANIm values between strain S30A2T and A. caldus KUT were 70.95 and 89.78 %, respectively and the digital DNA-DNA hybridization value was 24.9 %. Strain S30A2T was strictly aerobic and could utilize elementary sulphur and tetrathionate to support chemolithotrophic growth. The major cellular fatty acid of S30A2T was C19 : 1ω7c. The respiratory quinones were ubiquinone-8 and ubiquinone-7. Based upon its phylogenetic, genetic, phenotypic, physiologic and chemotaxonomic characteristics, strain S30A2T is considered to represent a novel species of the genus Acidithiobacillus, for which the name Acidithiobacillus acidisediminis sp. nov. is proposed. The type strain is S30A2T (=CGMCC 1.17059T=KCTC 72580T).

Genome-wide characterization and expression profiling of the HD-ZIP gene family in Acoraceae under salinity and cold stress.

The Homeodomain-Leucine Zipper (HD-ZIP) transcription factors play a pivotal role in governing various aspects of plant growth, development, and responses to abiotic stress. Despite the well-established importance of HD-ZIPs in many plants, their functions in Acoraceae, the basal lineage of monocots, remain largely unexplored. Using recently published whole-genome data, we identified 137 putative HD-ZIPs in two Acoraceae species, Acorus gramineus and Acorus calamus. These HD-ZIP genes were further classified into four subfamilies (I, II, III, IV) based on phylogenetic and conserved motif analyses, showcasing notable variations in exon-intron patterns among different subfamilies. Two microRNAs, miR165/166, were found to specifically target HD-ZIP III genes with highly conserved binding sites. Most cis-acting elements identified in the promoter regions of Acoraceae HD-ZIPs are involved in modulating light and phytohormone responsiveness. Furthermore, our study revealed an independent duplication event in Ac. calamus and a one-to-multiple correspondence between HD-ZIP genes of Ac. calamus and Ac. gramineus. Expression profiles obtained from qRT-PCR demonstrated that HD-ZIP I genes are strongly induced by salinity stress, while HD-ZIP II members have contrasting stress responses in two species. HD-ZIP III and IV genes show greater sensitivity in stress-bearing roots. Taken together, these findings contribute valuable insights into the roles of HD-ZIP genes in stress adaptation and plant resilience in basal monocots, illuminating their multifaceted roles in plant growth, development, and response to abiotic stress.

Associations of maternal liver biomarkers in the first trimester with the risk of hypertensive disorders of pregnancy.

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (Pinteraction = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP.

Spatiotemporal Expansion of Algal Blooms in Coastal China Seas.

The coastal seas of China are increasingly threatened by algal blooms, yet their comprehensive spatiotemporal mapping and understanding of underlying drivers remain challenging due to high turbidity and heterogeneous water conditions. We developed a singular value decomposition-based algorithm to map these blooms using two decades of MODIS-Aqua satellite data, spanning from 2003 to 2022. Our findings indicate significant algal activity along the Chinese coastline, impacting an average annual area of approximately 1.8 × 105 km2. The blooms exhibit peak intensity in August, while the maximum affected area occurs in September, featuring multifrequency outbreaks in spring, and pronounced large-scale events in summer and autumn. Notably, our analysis demonstrates a robust 67% increase in bloom occurrences over the study period. This expansion is primarily attributed to increased nutrient inflow from terrestrial sources linked to human activity and precipitation, compounded by rising global sea surface temperatures. These spatiotemporal insights are critical for devising effective management strategies and policies to mitigate the impacts of algal blooms.

Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer.

Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.

Comparison of double chevron-cut and biplanar distal femoral osteotomy techniques: A biomechanical study.

OBJECTIVE: This study aimed to compare the stability and mechanical properties of the double chevron-cut (DCC) and biplanar (BP) distal femoral osteotomy (DFO) techniques, along with analyzing their respective contact surface areas. METHODS: Biomechanical testing was performed using sawbone and 3D modeling techniques to assess axial and torsional stability, torsional stiffness, and maximum torque of both osteotomy configurations. Additionally, 3D models of the sawbone femur were created to calculate and compare the contact surface area of the DCC, BP, and conventional single-plane DFO techniques. RESULTS: Axial stiffness and maximum strength did not significantly differ between the two osteotomy techniques. However, in terms of torsional properties, the DCC technique exhibited superior torsional stiffness compared to the BP group (27 ± 7.7 Nm/° vs. 4.5 ± 1.5 Nm/°, p = 0.008). Although the difference in maximum torque did not reach statistical significance (63 ± 10.6 vs. 56 ± 12.1, p = 0.87), it is noteworthy that the DCC group sawbone model exhibited fracture in the shaft region instead of at the osteotomy site. Therefore, the actual maximum torque of the DCC construct may not be accurately reflected by the numerical values obtained in this study. The contact surface area analysis revealed that the BP configuration had the largest contact surface area, 111% larger than that of the single-plane configuration. but 60% of it relied on the less reliable axial cut. Conversely, the DCC osteotomy offered a 31% larger contact surface area than the single-plane configuration, with both surfaces being weight-bearing. CONCLUSION: The DCC osteotomy exhibited superior mechanical stability, showing improved rotational stiffness and maximum torque when compared to the BP osteotomy. Although the BP osteotomy resulted in a larger contact surface area than the DCC osteotomy, both were larger than the conventional single-plane configuration. In clinical practice, both the DCC and BP techniques should be evaluated based on patient-specific characteristics and surgical goals.

[Curcumin Combined with Thalidomide Inhibits Proliferation of KG-1 Cells and Its Related Mechanisms].

OBJECTIVE: To investigate the effects of curcumin combined with thalidomide on the proliferation and apoptosis of acute myeloid leukemia KG-1 cells, and its correlation with B-cell lymphoma-xL (Bcl-xL), signal transducer and activator of transcription 3 (STAT3). METHODS: MTT assay was used to detect the proliferation of KG-1 cells and screen the optimal combined concentration of curcumin and thalidomide. The effects of curcumin, thalidomide and their combination on the proliferation and apoptosis of KG-1 cells were analyzed by MTT method and flow cytometry, respectively. The mRNA expression levels of STAT3 and Bcl-xL in single-drug group, two-drug combination group and control group (untreated cells) were detected by real-time quantitative PCR. RESULTS: Both curcumin and thalidomide inhibited the proliferation of KG-1 cells in a concentration-dependent manner in the range of 20-100 µmol/L (r =0.657, r =0.681). The IC50 value of curcumin and thalidomide at 48 h was (42.07±0.50) µmol/L and (57.01±2.39) µmol/L, respectively. The cell proliferation inhibition rate of curcumin (40 µmol/L) + thalidomide (60 µmol/L) was (86.67±1.53)%, which was significantly higher than (51.67±1.15)% of curcumin (40 µmol/L) and (55.33±1.53)% of thalidomide (60 µmol/L) (both P < 0.05). Treated with curcumin and thalidomide alone or in combination, the apoptosis rate of KT-1 cells was (18.67±2.08)%, (21.33±2.52)%, and (46.67±1.53)%, respectively, which was significantly higher than (0.72±0.03)% of control group (all P < 0.05). The cell apoptosis rate of two-drug combination group was significantly higher than that of single-drug group (both P < 0.05). Compared with the control group, the mRNA expressions of STAT3 and Bcl-xL in single-drug group, two-drug combination group were significantly decreased (both P < 0.05). Compared with single-drug group, the mRNA expressions of STAT3 and Bcl-xL in two-drug combination group were also significantly decreased (both P < 0.05). CONCLUSION: Curcumin combined with thalidomide can synergistically down-regulate the expression of STAT3 and Bcl-xL, inhibit the proliferation of KG-1 cells, and induce apoptosis.

One Stone Three Birds: Silver Sulfadiazine Modulates the Stability and Dynamics of Hydrogels for Infected Wound Healing.

Dynamic covalent bond hydrogels have demonstrated significant application potential in biomedical fields for their dynamic reversibility. However, the contradiction between the stability and dynamics of the hydrogel restricts its application. Here, utilizing silver sulfadiazine (AgSD) as a catalyst, hyaluronic acid-based hydrogels are constructed through imine bond crosslinking and incorporated disulfide bonds within the same crosslinking chain. It is found that AgSD can accelerate the formation of imine crosslinking bonds to improve the stability of hydrogels, thereby shortening the gelation time by ≈36.9 times, enhancing compression strength and adhesion strength by ≈2.4 times and 1.7 times, respectively, while inhibiting swelling and degradation rates to ≈2.1 times and 3.7 times. Besides, AgSD can coordinate with disulfide bonds to enhance the dynamics of hydrogel, enhancing the hydrogel self-healing efficiency by ≈2.3 times while reducing the relaxation time by ≈25.1 times. Significantly, AgSD imparts remarkable antibacterial properties to the hydrogel, thereby effectively facilitating the healing of bacterial infected wounds. Consequently, introducing AgSD enables hydrogels to possess concurrent stability, dynamics, and antibacterial properties. This strategy of regulating hydrogels by introducing AgSD provides a valuable reference for the application of dynamic covalent bonds.

Genome-Wide Identification and Drought Stress Response Pattern of the NF-Y Gene Family in Cymbidium sinense.

Cymbidium sinense, a type of orchid plant, is more drought-resistant and ornamental than other terrestrial orchids. Research has shown that many members of the NUCLEAR FACTOR Y (NF-Y) transcription factor family are responsive to plant growth, development, and abiotic stress. However, the mechanism of the NF-Y gene family's response to abiotic stress in orchids has not yet been reported. In this study, phylogenetic analysis allowed for 27 CsNF-Y genes to be identified (5 CsNF-YAs, 9 CsNF-YBs, and 13 CsNF-YC subunits), and the CsNF-Ys were homologous to those in Arabidopsis and Oryza. Protein structure analysis revealed that different subfamilies contained different motifs, but all of them contained Motif 2. Secondary and tertiary protein structure analysis indicated that the CsNF-YB and CsNF-YC subfamilies had a high content of alpha helix structures. Cis-element analysis showed that elements related to drought stress were mainly concentrated in the CsNF-YB and CsNF-YC subfamilies, with CsNF-YB3 and CsNF-YC12 having the highest content. The results of a transcriptome analysis showed that there was a trend of downregulation of almost all CsNF-Ys in leaves under drought stress, while in roots, most members of the CsNF-YB subfamily showed a trend of upregulation. Additionally, seven genes were selected for real-time reverse transcription quantitative PCR (qRT-PCR) experiments. The results were generally consistent with those of the transcriptome analysis. The regulatory roles of CsNF-YB 1, 2, and 4 were particularly evident in the roots. The findings of our study may make a great contribution to the understanding of the role of CsNF-Ys in stress-related metabolic processes.

Sufentanil Suppresses Cell Carcinogenesis Via Targeting miR-186-5p/HMGB1 Axis and Wnt/ß-Catenin Pathway in Non-Small-Cell Lung Cancer.

Sufentanil is a common opioid anesthetic agent, which exerts anti-cancer properties in several cancer types. However, its action mechanisms in non-small cell lung cancer (NSCLC) are unclear. Therefore, the present study investigated the pharmacological effect of sufentanil on miRNAs in NSCLC treatment. In this study, after treatment with sufentanil, the proliferation, migration, invasion and apoptosis of A549 and H1299 NSCLC cell lines were measured by cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assays and flow cytometry. Quantitative real time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of miR-186-5p and high mobility group box-1 (HMGB1), and their interaction was analyzed using luciferase reporter assay. The proteins of HMGB1, and apoptosis- and Wnt/ß-catenin pathway-related factors were detected by western blot. It was demonstrated that sufentanil significantly upregulated miR­186­5p to restrict NSCLC cell proliferation, migration, invasion, and boost apoptosis in vitro. Mechanically, miR-186-5p interacted with HMGB1 and negatively regulated HMGB1 in NSCLC cells. Furthermore, rescue assay showed that sufentanil exerted antitumor activities by upregulating miR-186-5p, which targeted HMGB1 and restrained Wnt/ß-catenin signal pathway in NSCLC cells. In conclusion, these results suggested that sufentanil disrupts the oncogenicity of NSCLC cells by regulating miR-186-5p/HMGB1/ß-catenin axis, providing a promising implication for the anti-oncogenic effect of sufentanil.

Childhood vision impairment and blindness in West Africa: public health measures and implications for systemic health.

Childhood blindness is an issue of global health impact, affecting approximately 2 million children worldwide. Vision 2020 and the United Nations Sustainable Development Goals previously identified childhood blindness as a key issue in the twentieth century, and while public health measures are underway, the precise etiologies and management require ongoing investigation and care, particularly within resource-limited settings such as sub-Saharan Africa. We systematically reviewed the literature on childhood blindness in West Africa to identify the anatomic classification and etiologies, particularly those causes of childhood blindness with systemic health implications. Treatable causes included cataract, refractive error, and corneal disease. Systemic etiologies identified included measles, rubella, vitamin A deficiency, and Ebola virus disease. While prior public health measures including vitamin A supplementation and vaccination programs have been deployed in most countries with reported data, multiple studies reported preventable or reversible etiologies of blindness and vision impairment. Ongoing research is necessary to standardize reporting for anatomies and/or etiologies of childhood blindness to determine the necessity of further development and implementation of public health measures that would ameliorate childhood blindness and vision impairment.

Comprehensive Assessment of Environmental Emissions, Fate, and Risks of Veterinary Antibiotics in China: An Environmental Fate Modeling Approach.

China is one of the major global consumers of veterinary antibiotics. Insufficient recognition of emissions and environmental contamination hamper global efforts to prevent antibiotic resistance development. This pioneering study combined empirical data and modeling approaches to predict total 2010-2020 emissions of 80 veterinary antibiotics ranging from 23,110 to 40,850 tonnes/year, after 36-50% antibiotic removal by manure treatment. Following an initial increase of 10% from 2010 to 2015, emissions declined thereafter by 43%. While 85% of emissions discharged into soils, approximately 56%, 23%, and 18% of environmental residue were ultimately distributed in soils, freshwaters, and seawaters under steady-state conditions. In 2020, 657 (319-1470) tonnes entered the ocean from inland freshwaters. Median ∑antibiotics concentrations were estimated at 4.7 × 103 ng/L in freshwaters and 2.9 ng/g in soils, with tetracyclines and sulfonamides as the predominant components. We identified 44 veterinary antibiotics potentially posing high risks of resistance development in freshwaters, with seven exhibiting high risks in >10% of Chinese freshwater areas. Tetracyclines were the category with the most antibiotics exhibiting elevated risks; however, sulfamethylthiazole demonstrated the highest individual compound risk. The Haihe River Basin displayed the highest susceptibility overall. The findings offer valuable support for control of veterinary antibiotic contamination in China.