GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells.

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1ß and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100A8/9 expression.

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis (UC), and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development. Here, we find that the IL-17 receptor subunit, CMTM4, is reduced in UC patients and dextran sulfate sodium (DSS)-induced colitis. The deletion of CMTM4 (Cmtm4-/-) in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type, and the gut microbiome significantly changes in composition. The causal role of the gut microbiome is confirmed with a cohousing experiment. We further identify that S100a8/9 is significantly up-regulated in Cmtm4-/- colitis, with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency. CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway, further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis. Taken together, the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis, suppression of S100a8/9, and prevention of colitis development. Our study further shows CMTM4 as a crucial innate immunity component, confirming its important role in the UC development and providing insights into potential targets for the development of future therapies.

Assessment of Wound-Related Pain Experiences of Patients With Chronic Wounds: A Multicenter Cross-Sectional Study in Eastern China.

PURPOSE: The primary aims of this study were to evaluate the prevalence of wound-related pain (WRP) in patients with chronic wounds and assess the use of pain relief measures. DESIGN: A cross-sectional study. SUBJECTS AND SETTING: A convenience sample of patients with chronic wounds was recruited from outpatient clinics of 12 hospitals covering 7 of 13 cities in the Jiangsu province located in eastern China from July 10 to August 25, 2020. The sample comprised 451 respondents, and their mean age was 54.85 (SD 19.16) years; 56.1% (253/451) patients were male. METHODS: An investigator-designed questionnaire was used to collect pain-related information from patients. The questionnaire consisted of 4 parts: (1) basic demographic and clinical information (patient and wound characteristics); (2) wound baseline pain; (3) wound-related procedural pain and pain relief method; and (4) the effect of WRP on the patient. Pain was assessed using the Numerical Rating Scale (NRS) scored from 0 (no pain) to 10 (worst pain). Severity of pain was based on NRS scores' classification as mild (1-3), moderate (4-6), and severe (7-10). The survey was conducted from July 10 to August 25, 2020. Participants were instructed on use of the NRS and then completed the questionnaire following dressing change independently. RESULTS: The 3 most common types of chronic wounds were traumatic ulcers, surgical wounds, and venous leg ulcers. The 3 most prevalent locations were lower limbs, feet, and thorax/abdomen. Of all patients, 62.5% (282/451) and 93.8% (423/451) patients experienced wound baseline pain and wound-related procedural pain, respectively. The mean score of wound baseline pain was 3.76 (SD 1.60) indicating moderate pain. During wound management, the highest pain score was 6.45 (SD 2.75) indicating severe pain; the most severe pain scores were associated with debridement. The use of drugs to relieve wound pain was low, while the use of nondrug-based analgesia was relatively high. Because of WRP, patients with chronic wounds feared dressing changes, hesitated to move, and showed a decline in sleep quality. CONCLUSIONS: Wound baseline pain and wound-related procedural pain were very common in patients with chronic wounds. In the future, targeted intervention plans should be developed by combining drug-based and nondrug-based analgesia according to pain severity.

Microstructure engineering in sulfuretted coal tar pitch by varying the Cross-Link state for enhanced sodium storage.

Sulfur (S) is an efficient dopant to enhance the sodium storage of carbon, yet the conventional in-situ/post treatments cause unstable S configuration or lower S content, and hence unsatisfied electrochemical performance. Herein, we investigate sulfurization at various cross-link state of coal tar pitch (CTP) (pristine, coke, and carbonized states), and the microstructure of the products (SCTP). Experimental and calculational results reveal that introducing S in the coke state of CTP is essential for achieving abundant and stable C-Sx-C bonds between carbon layers. Moreover, this innovative strategy not only achieves a high S content, but also avoids the liquid carbonization, resulting in a hierarchically porous structure with a small particle size. As a result, the SCTP delivers a sodium storage capacity of 318 mA h g-1 at 0.1 A g-1 after 200th cycle, and the capacity maintains 207 mA h g-1 with capacity retention of 99 % after 1000th cycle at 2.0 A g-1, in half-cells. Moreover, the sample shows a considerable discharge capacity of 328 mA h g-1anode at 0.05 A g-1 in full-cells. Consequently, this approach offers a novel pathway for large-scale production of thermoplastic-derived carbons in battery industry.

Ferroptosis and Preeclampsia: Genetic Analysis of Potential Biomarkers and Therapeutic Targets.

Ferroptosis is the oxidative death of cells attributed to an imbalance in intracellular lipid reactive oxygen species metabolism, a reduction in cell antioxidant capacity, and an accumulation of membrane lipid peroxides. Trophoblast cells are a group of cells susceptible to ferroptosis. The ferroptosis of trophoblast cells has a major effect on the development of preeclampsia (PE), although the impact of ferroptosis-related genes (FRGs) on PE has not been well characterized. This study obtained PE-related information from the Gene Expression Omnibus database and FRGs from the FerrDb ferroptosis database. Seventeen PE-related differentially expressed ferroptosis-related genes (DE-FRGs) that were closely associated with cellular regulation and immune response were obtained. According to the results of a subsequent functional enrichment analysis, it was found that the above marker genes may impact PE by regulating immune response, amino acid metabolism, the cell cycle, and multiple pathways correlated with PE pathogenesis. Subsequently, we used LASSO and support vector machine recursive feature elimination algorithms to help identify GOT1, CFL1, FZD7, VDR, PARP6, TMSB4X, VCP, and ENO3 as marker genes from the 17 obtained genes. According to the results of single-sample gene set enrichment analysis (ssGSEA), the immune microenvironment of PE changed, possibly due to the GOT1 and TMSB4X genes. Furthermore, 23 drugs targeting one marker gene were determined. A constructed ceRNA network revealed a complicated regulatory link based on the eight marker genes. In this study, diagnostic potency was developed, and insight into the mechanism of PE was provided. In-depth research should be conducted before clinical application to evaluate the diagnostic value of DE-FRGs in PE.

Treatment of lactational mastitis with Gualou Xiaoyong soup and painless lactation promoting technique: A case series.

BACKGROUND: Lactational mastitis is a common and frequently disease in clinical practice, characterized by acute inflammation of the mammary ducts and surrounding connective tissues. The main manifestations are damage to the mammary gland acini, edema, and invasion of inflammatory cells. If not treated properly, it may lead to the formation of breast abscesses, or even sepsis, septic shock, and chronic inflammation of the breast, which may cause the disease to persist or recur multiple times, so that the patients suffer extreme pain, and the health of both the mother and child are directly affected. This disease not only causes suffering for women but also may result in the cessation of breastfeeding. Therefore, rapid and effective treatment is particularly important. CASE SUMMARY: We report 3 cases of lactation mastitis patients showing good clinical efficacy after being treated with the Chinese medicine Gualou Xiaoyong soup and painless lactation promoting techniques. Gualou Xiaoyong soup combined with painless lactation promotion techniques can significantly reduce and eliminate the clinical symptoms of patients in the short term, and rapidly restore inflammatory indicators such as total white blood cells, neutrophils, C-reactive protein, and procalcitonin to normal levels. The patchy low echo area of the breast under B-ultrasound also disappears quickly. Therefore, we believe that this method is a good way to treat lactational mastitis and is worthy of clinical reference and research. However, this study has certain limitations: this study lacks a large sample of prospective controlled studies. Next, we will continue to collect relevant cases and conduct prospective case randomized controlled clinical studies. CONCLUSION: The treatment of lactation mastitis with Gualou Xiaoyong soup and painless lactation promoting techniques can achieve good clinical results.

Sanji Peiyuan decoction combined with dydrogesterone in the treatment of massive subchorionic hematoma: A case report.

RATIONALE: Subchorionic Hematoma, often referred to as Bruce hematoma, can lead to serious obstetric complications such as intrauterine growth restriction and fetal death, as well as early and late pregnancy miscarriage, placental abruption, and premature rupture of membranes, posing great harm to both mother and fetus. PATIENT CONCERNS: At present, Western medical treatments have not shown satisfactory results, necessitating the discovery of more effective clinical treatment methods. DIAGNOSES: Threatened miscarriage, Subchorionic hematoma, Iron deficiency anemia (mild). INTERVENTIONS: Sanji Peiyuan decoction combined with dydrogesterone. OUTCOMES: Following 17 days of treatment with Sanji Peiyuan decoction and oral dydrogesterone tablets, the hematoma was no longer detectable by ultrasound. The patient experienced no symptoms such as abdominal pain, bloating, or vaginal bleeding. She successfully gave birth around her due date, with both the mother and child in good health. LESSONS: The combination of Sanji Peiyuan decoction and oral dydrogesterone tablets shows promising clinical efficacy in treating Massive Subchorionic Hematomas. This method merits further clinical research.

Association of Neutrophil and Albumin With Mortality Risk in Patients Receiving Peritoneal Dialysis.

OBJECTIVE: Inflammation and nutrition have been recognized as predicting mortality in patients receiving peritoneal dialysis (PD). Serum neutrophil and albumin are crucial factors in inflammation and nutrition status. Up until now, the synergistic effect of neutrophil and albumin on mortality prediction in PD patients is still being determined. Our study sought to assess the effect of the interaction between neutrophils and albumin on the risk of all-cause mortality and cardiovascular disease (CVD) mortality patients receiving PD. METHODS: A total of 1229 PD patients were recruited and divided into three categories in this cohort study. Their relationships with all-cause mortality and CVD mortality were analyzed in multivariable COX regression models adjusted for confounding factors. RESULTS: During the median follow-up of 34.2 months, 222 (18.1%) patients died, and 115 (51.8%) suffered from cardiovascular events. Patients with high neutrophil percentage-to-albumin ratio (NPAR) showed increased all-cause mortality and CVD mortality, with adjusted hazard ratios of 1.490 (95% confidence interval, 1.070-2.074, P = .018) and 1.633 (95% confidence interval, 1.041-2.561, P = .033), respectively, compared with those with low NPAR. Competitive risk models and sensitivity analyses further confirmed this association. In the receiver operating characteristic curve analysis, however, there was little evidence that NPAR is a better indicator than albumin and neutrophil count. CONCLUSIONS: Having a high NPAR is linked to a higher risk of mortality, especially when both high neutrophil and low albumin are present.

Clinical efficacy of Gualou Xiaoyong Decoction and painless lactation manipulation in treating lactation acute mastitis and breast abscess: An observational study.

Information on the effects of Chinese medicine in the treatment of lactational acute mastitis and breast abscess is limited; thus, we conducted an observational study to analyze the clinical efficacy of Gualou Xiaoyong Decoction combined with painless lactation manipulation in the treatment of lactational acute mastitis and breast abscess. A total of 41 patients with lactational acute mastitis and breast abscess who were treated with Gualou Xiaoyong Decoction and painless lactation manipulation from October 2021 to October 2022 were included in this study. The age, fetal times(primiparous/multiparous), delivery mode (cesarean section/vaginal delivery), onset time, breast lump diameter, skin rash diameter, body temperature, visual analogue score, blood routine, C-reactive protein, procalcitonin, bacterial culture in milk, B ultrasound and other data of these patients were statistically analyzed. After treatment, the breast lump diameter of these patients decreased significantly, the skin rash diameter was reduced or disappeared, the body temperature decreased or returned to a normal range, and the visual analogue score also decreased. Besides, these patients had a decreased total number of white blood cells and a reduced percentage of neutrophils, C-reactive protein, and procalcitonin after treatment. In addition, bacteria in the milk of most patients disappeared, and there was no abnormality in B ultrasonic imaging. Except for 2 patients with breast abscess who stopped breastfeeding on the affected side for 1 day and 3 days respectively, all other patients continued to provide breast milk for their infants, and no adverse reactions were observed in these infants. The combination of Gualou Xiaoyong Decoction and painless lactation manipulation can achieve favorable clinical effects in the treatment of lactational acute mastitis and breast abscess. This combined therapy has good efficacy, short course of treatment, low costs, and great convenience with the avoidance of pain, hospitalization, influence on lactation, breast scar and other adverse outcomes.

CircRNA_0088196 Regulates Trophoblast Proliferation and Apoptosis in Preeclampsia Through the miR-379-5p/HSPA5 Axis.

Existing research has confirmed the dysregulation of circular RNA (circRNA) in a wide variety of human diseases. Thus, in this study, we explored the potential mechanism of circRNA_0088196 in preeclampsia (PE). We performed quantitative real-time PCR to examine circRNA_0088196 expression and verified the function of circRNA_0088196 in vitro using CCK-8, TUNEL, flow cytometry, and Western blotting analyses. Additionally, we studied the mechanism using dual-luciferase reporter gene experiments. The results of our research revealed the up-regulation of circRNA_0088196 in PE patients' placentas and Heat Shock 70 kDa Protein 5 (HSPA5)-stimulated trophoblast (HTR-8/SVneo) cells. An investigation of the mechanism also showed that there was a binding between miR-379-5p and circRNA_0088196. Additionally, circRNA_0088196 inhibited HTR-8/SVneo cell proliferation and promoted cell apoptosis via the miR-337-3p/HSPA5 axis, thereby facilitating PE. In vivo experiments indicated that circRNA_0088196 regulated HTR-8/SVneo cell production through miR-379-5p. Overall, the findings of this study illustrate that circRNA_0088196 interference promotes cell apoptosis and inhibits HTR-8/SVneo proliferation via the miR-379-5p/HSPA5 axis, thereby accelerating the development of PE.

RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation.

The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves not only as a bicistronic message RNA to translate core protein (Cp) and DNA polymerase (Pol), but also as the template for reverse transcriptional replication of viral DNA upon packaging into nucleocapsid. Although it is well known that pgRNA translates much more Cp than Pol, the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive. In this study, we systematically profiled HBV nucleocapsid- and pgRNA-associated cellular proteins by proteomic analysis and identified TIA-1-related protein (TIAR) as a novel cellular protein that binds pgRNA and promotes HBV DNA replication. Interestingly, loss- and gain-of-function genetic analyses showed that manipulation of TIAR expression did not alter the levels of HBV transcripts nor the secretion of HBsAg and HBeAg in human hepatoma cells supporting HBV replication. However, Ribo-seq and PRM-based mass spectrometry analyses demonstrated that TIAR increased the translation of Pol but decreased the translation of Cp from pgRNA. RNA immunoprecipitation (RIP) and pulldown assays further revealed that TIAR directly binds pgRNA at the 5' stem-loop (ε). Moreover, HBV replication or Cp expression induced the increased expression and redistribution of TIAR from the nucleus to the cytoplasm of hepatocytes. Our results thus imply that TIAR is a novel cellular factor that regulates HBV replication by binding to the 5' ε structure of pgRNA to tip the balance of Cp and Pol translation. Through induction of TIAR translocation from the nucleus to the cytoplasm, Cp indirectly regulates the Pol translation and balances Cp and Pol expression levels in infected hepatocytes to ensure efficient viral replication.

The A1762T/G1764A mutations enhance HBV replication by alternating viral transcriptome.

The A1762T/G1764A mutations, one of the most common mutations in the hepatitis B virus basal core promoter, are associated with the progression of chronic HBV infection. However, effects of these mutations on HBV replication remains controversial. This study aimed to systematically investigate the effect of the mutations on HBV replication and its underlying mechanisms. Using the prcccDNA/pCMV-Cre recombinant plasmid system, a prcccDNA-A1762T/G1764A mutant plasmid was constructed. Compared with wild-type HBV, A1762T/G1764A mutant HBV showed enhanced replication ability with higher secreted HBV DNA and RNA levels, while Southern and Northern blot indicated higher intracellular levels of relaxed circular DNA, single-stranded DNA, and 3.5 kb RNA. Meanwhile, the mutations increased expression of intracellular core protein and decreased the production of HBeAg and HBsAg. In vitro infection based on HepG2-NTCP cells and mice hydrodynamic injection experiment also proved that these mutations promote HBV replication. 5'-RACE assays showed that these mutations upregulated transcription of pregenomic RNA (pgRNA) while downregulating that of preC RNA, which was further confirmed by full-length transcriptome sequencing. Moreover, a proportion of sub-pgRNAs with the potential to express polymerase were also upregulated by these mutations. The ChIP-qPCR assay showed that A1762T/G1764A mutations created a functional HNF1α binding site in the BCP region, and its overexpression enhanced the effect of A1762T/G1764A mutations on HBV. Our findings revealed the mechanism and importance of A1762T/G1764A mutations as an indicator for management of CHB patients, and provided HNF1α as a new target for curing HBV-infected patients.

Molecular Mechanism of the Therapeutic Effect of Peach Blossom against Constipation: An Exploratory Study Based on Network Pharmacology Analysis and Molecular Docking Verification.

Objective: The aim of the study is to verify the active ingredients of peach blossom and to explore the molecular mechanisms of their therapeutic effects against constipation through network pharmacology and molecular docking analysis. Methods: The potential active ingredients of peach blossom were identified from published literature and the BAT-TCM database, and their potential targets were predicted using the SwissTargetPrediction and PharmMapper platforms. In addition, targets related to constipation were retrieved using OMIM, DrugBank, GeneCards, TTD, and DisGeNET databases. The intersection of drug targets and disease targets was considered as the potential targets of peach blossom in the treatment of constipation. The STRING platform was used to construct a protein interaction network. Gene ontology (GO) functional analysis and KEGG pathway enrichment analysis were performed on key targets using the DAVID database. Molecular docking verification between the active ingredients of peach blossom and the targets was conducted using AutoDock software. Results: A total of 33 active ingredients of peach blossom and 185 corresponding targets were identified, and 88 intersection targets were obtained after Venny mapping. These 33 active ingredients (including naringenin, aromadendrin, and cordycepin) in peach blossom may play a role in the treatment of constipation by regulating signaling pathways through targets such as EGFR, VEGFA, ESR1, GSTP1, and PTGS2. Conclusion: A variety of active ingredients of peach blossom regulate multiple signaling pathways by acting on targets, which reflects the characteristic of "multiple ingredients-multiple targets-multiple pathways," thereby playing a role in the treatment of constipation.

Lactation breast abscess treated with Gualou Xiaoyong decoction and painless lactation manipulation: A case report and review of literature.

BACKGROUND: Breast abscess during lactation is a severe complication of acute mastitis, which can lead to discomfort, high fever, breast fistula, sepsis, septic shock, breast damage, disease persistence and frequent hospitalization. Breast abscesses may also lead the mother to discontinue breastfeeding, thereby harming the infant's health. The predominant pathogenic bacteria are Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus. The incidence of breastfeeding abscesses in breastfeeding women ranges between 4.0% and 11.0%. In cases of breast abscess, the rate of cessation of lactation is 41.0%. In instances of breast fistula, the rate of cessation of lactation is very high (66.7%). Furthermore, 50.0% of women with breast abscesses must be hospitalized and treated with intravenous antibiotics. Treatment includes antibiotics, abscess puncture and surgical incision and drainage. The patients suffer from stress, pain and easily induced breast scarring; the disease's progression is prolonged and recurrent, interfering with infant feeding. Consequently, it is crucial to discover an adequate cure. CASE SUMMARY: A 28-year-old woman with a breast abscess was treated with Gualou Xiaoyong decoction and painless breast opening manipulation 24 d after cesarean delivery. On the 2nd d of treatment, the patient's breast mass was significantly reduced, the pain was significantly reduced, and the general asthenia was improved. All conscious symptoms disappeared after 3 d, breast abscesses faded after 12 d of treatment, inflammation images disappeared after 27 d, and normal lactation images were restored. CONCLUSION: In treating breast abscesses during breastfeeding, the combination of Gualou Xiaoyong decoction and painless lactation provides a positive therapeutic impact. This disease's treatment offers the advantages of a short course of treatment, no need to discontinue breastfeeding and the ability to rapidly mitigate symptoms, which can be used as a reference in clinical practice.

Modulation of Bi3+ luminescence from broadband green to broadband deep red in Lu2WO6 by Gd3+ doping and its applications in high color rendering index white LED and near-infrared LED.

Phosphors that exhibit tunable broadband emissions are highly desired in multi-functional LEDs, including pc-WLEDs and pc-NIR LEDs. In this work, broadband emissions were obtained and modulated in the unexpectedly wide spectral range of 517-609 nm for (Lu0.99-xGdxBi0.01)2WO6 phosphors by tuning the Gd3+ content (x = 0-0.99). The effects of Gd3+ doping on phase constituents, particle morphology, crystal structure, and photoluminescence were systematically investigated. Broadband green emission was obtained from Gd3+-free (Lu0.99Bi0.01)2WO6 phosphors (x = 0), whose emission intensity was enhanced by 50% with 5 at% Gd3+ (x = 0.05). The phase transition happened when x > 0.50 and the broadband red-NIR emission was obtained when x = 0.75-0.99. Three luminescence centers were proved to be responsible for the broadband green emissions via crystal structure, spectral fitting and fluorescence decay analysis. A pc-WLED with a high color rendering index (Ra = 91.3), a stable emission color, and a low color temperature (3951 K) was fabricated from the (Lu0.94Gd0.05Bi0.01)2WO6 broadband green phosphor, and an LED device that simultaneously emits high color rendering index white light and NIR light was obtained with the (Gd0.99Bi0.01)2WO6 broadband red-NIR phosphor. Night vision and noninvasive imaging were also demonstrated using the latter LED device.

Design and characterization of a high-resolution multiple-SNP capture array by target sequencing for sheep.

The efficiency of molecular breeding largely depends on inexpensive genotyping arrays. In this study, we aimed to develop an ovine high-resolution multiple-single-nucleotide polymorphism (SNP) capture array, based on genotyping by target sequencing (GBTS) system with capture-in-solution (liquid chip) technology. All the markers were from 40K captured regions, including genes located within selective sweep regions, breed-specific regions, quantitative trait loci (QTL), and the potential functional SNPs on the sheep genome. The results showed that a total of 210K high-quality SNPs were identified in the 40K regions, indicating a high average capture ratio (99.7%) for the target genomic regions. Using genotyped data (n = 317) from liquid chip technology, we further performed genome-wide association studies (GWAS) to detect the genetic loci affecting sheep hair types and teat number. A single significant association signal for hair types was identified on 6.7-7.1 Mb of chromosome 25. The IRF2BP2 gene (chr25: 7,067,974-7,071,785), which is located within this genomic region, has been previously known to be involved in hair/wool traits in sheep. The results further showed a new candidate region around 26.4 Mb of chromosome 13, between the ARHGAP21 and KIAA1217 genes, that was significantly related to teat number in sheep. The haplotype patterns of this region also showed differences in animals with 2, 3, or 4 teats. Advances in using the high-accuracy and low-cost liquid chip are expected to accelerate sheep genomic and breeding studies in the coming years.

Large-scale genotyping platforms are valuable tools for animal selection and breeding programs. The bead chip has been widely used in both research and commercial applications for a long time. A highly efficient and economical genotyping platform has been developed recently. In the present study, by combining the advantages of resequencing and bead chips, we developed a high-resolution capture array based on target sequencing with capture-in-solution technology (liquid chip), including updated functional probes according to the latest research. We further evaluated this approach by using 317 individuals and found that 210K single-nucleotide polymorphisms can be accurately genotyped, confirming the ratio of the captured regions compared with the designed rations is around 99.7%. Genome-wide association studies conducted using this chip suggested IRF2BP2 gene may be involved in hair types and ARHGAP21-KIAA1217 locus may be related to teats number. The liquid chip with high accuracy and low cost can be widely used in genome-wide association studies and genome selection, supporting efforts in molecular breeding and genetic improvement of sheep.

COVID-19 pharmacological research trends: a bibliometric analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic is ravaging the world. Many therapies have been explored to treat COVID-19. This report aimed to assess the global research trends for the development of COVID-19 therapies. Methods: We searched the relevant articles on COVID-19 therapies published from January 1, 2020, to May 25, 2022, in the Web of Science Core Collection Database (WOSCC). VOSviewer 1.6.18 software was used to assess data on the countries, institutions, authors, collaborations, keywords, and journals that were most implicated in COVID-19 pharmacological research. The latest research and changing trends in COVID-19-relevant pharmacological research were analyzed. Results: After manually eliminating articles that do not meet the requirements, a total of 5,289 studies authored by 32,932 researchers were eventually included in the analyses, which comprised 95 randomized controlled trials. 3,044 (57.6%) studies were published in 2021. The USA conducted the greatest number of studies, followed by China and India. The primary USA collaborators were China and England. The topics covered in the publications included: the general characteristics, the impact on pharmacists' work, the pharmacological research, broad-spectrum antiviral drug therapy and research, and promising targets or preventive measures, such as vaccine. The temporal diagram revealed that the current research hotspots focused on the vaccine, molecular docking, Mpro, and drug delivery keywords. Conclusion: Comprehensive bibliometric analysis could aid the rapid identification of the principal research topics, potential collaborators, and the direction of future research. Pharmacological research is critical for the development of therapeutic and preventive COVID-19-associated measures. This study may therefore provide valuable information for eradicating COVID-19.

The tibetan medicine Zuozhu-Daxi can prevent Helicobacter pylori induced-gastric mucosa inflammation by inhibiting lipid metabolism.

BACKGROUND: Tibetan medicine has been used in clinical practice for more than 3800 years. Zuozhu-Daxi (ZZDX), a classic traditional Tibetan medicine, has been proved to be effective in the treatment of digestive diseases, such as chronic gastritis, gastric ulcer, etc. Helicobacter pylori (H. pylori), one of the most common pathogenic microbes, is regarded as the most common cause of gastritis. Researching on the effects of ZZDX on H. pylori-induced gastric mucosa inflammation could provide more evidences on H. pylori treatment and promote the development of Tibetan medicine. This study aimed to explore whether ZZDX could rescue H. pylori-induced gastric mucosa inflammation and its mechanism. METHODS: Male C57BL/6 mice were infected with H. pylori, and orally treated with ZZDX to rescue gastric mucosa inflammation induced by H. pylori infection. Pathology of gastric mucosa inflammation was evaluated under microscopy by hematoxylin-eosin (HE) staining. The infection status of H. pylori was evaluated by immunohistochemical (IHC) staining. The reactive oxygen species (ROS) level in serum was evaluated using a detection kit. IL-1α, IL-6, and PGE2 expression levels in serum were measured using ELISA. IL-1α, IL-8, TNF-α, and NOD1 expression levels in gastric tissues were measured using real-time PCR. RNA sequencing and gene certification of interest were performed to explore the mechanisms in vivo and in vitro. RESULTS: The results showed that ZZDX could significantly inhibit H. pylori-induced gastric mucosa inflammation using HE staining. IL-1α, IL-6, and PGE2 expression levels in serum were significantly decreased after treatment with ZZDX. ZZDX treatment significantly decreased the mRNA expression of IL-8 induced by H. pylori infection in gastric tissues. Elovl4, Acot1 and Scd1 might be involved in the mechanisms of ZZDX treatment. However, the H. pylori infection status in the gastric mucosa was not reduced after ZZDX treatment. CONCLUSIONS: ZZDX reversed gastric mucosal injury and alleviated gastric mucosa inflammation induced by H. pylori infection.

Pd Metallene Aerogels with Single-Atom W Doping for Selective Ethanol Oxidation.

The development of advanced electrocatalysts with satisfactory C1 pathway selectivity for the ethanol oxidation reaction (EOR) is critical. Herein, a bubbling CO-induced gelation method is developed in acetic acid at 50 °C to construct single-atom W-doped Pd metallene aerogels (denoted as SA W-Pd MAs) within 1 h. In light of the metallene structural advantages of noble metal aerogels and single-atom W decoration, the resultant SA W-Pd MAs exhibit an outstanding EOR performance with high C1 pathway selectivity. Density functional theory calculations validate that the SA W-Pd MAs greatly improve the formation of the CH3O intermediate and the transformation of poisonous CO species to CO2, thus resulting in high C1 pathway selectivity. Therefore, this work not only offers an effective gelation method to fabricate noble metal aerogels with atomic-scale building blocks but also presents guidance to develop high-efficiency EOR electrocatalysts.

In vitro transdifferentiated signatures of goat preadipocytes into mammary epithelial cells revealed by DNA methylation and transcriptome profiling.

During mammary development, the transdifferentiation of mammary preadipocytes is one of the important sources for lactating mammary epithelial cells (MECs). However, there is limited knowledge about the mechanisms of dynamic regulation of transcriptome and genome-wide DNA methylation in the preadipocyte transdifferentiation process. Here, to gain more insight into these mechanisms, preadipocytes were isolated from adipose tissues from around the goat mammary gland (GM-preadipocytes). The GM-preadipocytes were cultured on Matrigel in conditioned media made from goat MECs to induce GM-preadipocyte-to-MEC transdifferentiation. The transdifferentiated GM-preadipocytes showed high abundance of keratin 18, which is a marker protein of MECs, and formed mammary acinar-like structures after 8 days of induction. Then, we performed transcriptome and DNA methylome profiling of the GM-preadipocytes and transdifferentiated GM-preadipocytes, respectively, and the differentially expressed genes and differentially methylated genes that play underlying roles in the process of transdifferentiation were obtained. Subsequently, we identified the candidate transcription factors in regulating the GM-preadipocyte-to-MEC transdifferentiation by transcription factor-binding motif enrichment analysis of differentially expressed genes and differentially methylated genes. Meanwhile, the secretory proteome of GM-preadipocytes cultured in conditioned media was also detected. By integrating the transcriptome, DNA methylome, and proteome, three candidate genes, four proteins, and several epigenetic regulatory axes were further identified, which are involved in regulation of the cell cycle, cell polarity establishment, cell adhesion, cell reprogramming, and adipocyte plasticity. These findings provide novel insights into the molecular mechanism of preadipocyte transdifferentiation and mammary development.