The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

Validation of China Health-Related Outcomes Measures-Cardiovascular Disease.

OBJECTIVES: China Health-Related Outcomes Measures (CHROME) was an initiative aimed at developing a system of preference-based health-related quality of life instruments for China. CHROME-cardiovascular disease (CVD) is a CVD-specific instrument with 14 items developed under this initiative. This study aimed to test the psychometric properties of CHROME-CVD. METHODS: This validation study was conducted using cross-sectional questionnaire survey in China. Eligible patients with CVD were recruited and asked to complete the CHROME-CVD, the EQ-5D-5L, and a CVD-specific nonpreference-based health-related quality of life instrument selected according to the confirmed diagnosis of the patients. Item evaluation, internal consistency, measurement invariance, test-retest reliability, structural validity, and construct validity were tested using classic test theory. Item response theory was used to evaluate item-level performance. RESULTS: A total of 444 patients with CVD (coronary artery disease, n = 276, heart failure, n = 104, angina, n = 33, and atrial fibrillation, n = 16) from 6 provinces in China were enrolled for the validation. Exploratory factor analysis identified 4 factors: chest pain, other symptoms, physical health, and mental and social health. Cronbach's alpha and intraclass correlation coefficient were >0.8. A total of 20 of 26 (76.9%), and 90 of 95 (94.7%) predefined hypotheses were met for convergent and discriminant validities, respectively. No important difference was identified between subgroups of gender and residency. Response options of 10 items were found overlapped based on categorical response curves, which led to modification to 4-level response options. Wording of 3 items were modified by referring wordings of reference instruments. CONCLUSION: The validation of the CHROME-CVD demonstrated generally good psychometric properties. Further validation on the modified CHROME-CVD is needed.

Correlation between lipoprotein(a) and recurrent ischemic events post-cerebral vascular stent implantation.

BACKGROUND AND AIM: The association of Lipoprotein(a) (Lp[a]) with recurrent ischemic events in stented patients remains uncertain. So, this research aimed to investigate the impact of elevated Lp(a) levels on the occurrence of ischemic events in this specific patient population. METHODS: Totally 553 patients who underwent intracranial or extracranial artery stent implantation were included. Baseline data were collected and postoperative ischemic outcomes were followed up. Cox regression analysis was used to investigate the association between Lp(a) and outcomes, while accounting for confounding factors. Finally, we established prediction models based on nomogram. RESULTS: Of total 553 patients, a number of 107 (19.3%) experienced outcomes. These included 46 cases (25.4%) in group with elevated Lp(a) levels (>30 mg/dL) and 61 cases (16.4%) in non-elevated group (χ2=6.343, p=0.012). The group with elevated Lp(a) was 1.811 times more likely to experience ischemic events than the non-elevated group, each 1 mg/dL increase in Lp(a) resulted in a 1.008-fold increase in the recurrence rate of ischemic events. In addition, sex (male), previous history of coronary heart disease, decreased albumin, elevated very low density lipoprotein cholesterol and poorly controlled risk factors (including blood pressure and blood sugar) were also associated with a high risk of recurrent ischemic events after stent implantation. CONCLUSION: Lp(a) elevation was a significant risk factor for ischemic events in symptomatic patients who underwent intracranial or extracranial artery stenting.

Enhanced Fire Safety of Energy-Saving Foam by Self-Cleavage CO2 Pre-Combustion and Phosphorus Release Post-Combustion.

Rigid polyurethane foam (RPUF) is widely utilized in construction and rail transportation due to its lightweight properties and low thermal conductivity, contributing to energy conservation and emission reduction. However, the inherent flammability of RPUF presents significant challenges. Delaying the time to ignition and preventing flame spread post-combustion is crucial for ensuring sufficient evacuation time in the event of a fire. Based on this principle, this study explores the efficacy of using potassium salts as a catalyst to promote the self-cleavage of RPUF, generating substantial amounts of CO2, thereby reducing the local oxygen concentration and delaying ignition. Additionally, the inclusion of a reactive flame retardant (DFD) facilitates the release of phosphorus-oxygen free radicals during combustion, disrupting the combustion chain reaction and thus mitigating flame propagation. Moreover, potassium salt-induced catalytic carbonization and phosphorus derivative cross-linking enhance the condensed phase flame retardancy. Consequently, the combined application of potassium salts and DFD increases the limiting oxygen index (LOI) and reduces both peak heat release rate (PHRR) and total heat release (THR). Importantly, the incorporation of these additives does not compromise the compressive strength or thermal insulation performance of RPUF. This integrated approach offers a new and effective strategy for the development of flame retardant RPUF.

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma-an exploration of surrogate endpoint.

BACKGROUND: Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy. METHODS: Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation. RESULTS: PFS correlated moderately with OS in the retrospective cohort (Kendall's Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group. CONCLUSION: In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.

Utilization of feather keratin waste to antioxidant and migration-enhancer peptides by Bacillus licheniformis 8-4.

AIMS: Feathers are keratin-rich byproducts of poultry processing, but those are often frequently abandoned as garbage and thus polluting the environment. Therefore, the study focused on the efficient biodegradation, bioactivity, and high-value application of feather keratin. METHODS AND RESULTS: Feather-degrading bacteria were identified, and the degradation properties were characterized. DPPH (1,1-Diphenyl-2-picrylhydrazyl radical) and ABTS (2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid))radical scavenging assays, cytotoxicity assays, intracellular reactive oxygen scavenging assays, and cell migration assays were used to examine the biological activities of the feather keratin hydrolysis peptides (FKHPs). The results showed that we screened a feather-degrading strain of Bacillus licheniformis 8-4, which achieved complete degradation of 2% (w/v) feathers within 48 h. Notably, the feather fermentation broth was particularly high in FKHPs, which exhibited good DPPH and ABTS radical scavenging ability. Further studies revealed that FKHPs had both the ability to scavenge H2O2-induced ROS from HaCat cells and the ability to promote HaCat cell migration, while remaining non-toxic. CONCLUSIONS: The effective feather-degrading ability of B. licheniformis 8-4 allowed for the fermentation of feather medium to yield active peptides that were both antioxidants and cell-migration enhancers.

Effect of social integration on family doctor contracting services among migrant populations in China: a national cross-sectional survey.

BACKGROUND: The family doctor (FD) contracting system is a key reform in the development of the Chinese health system, and is considered an effective way to ensure equitable access to healthcare services. This study investigates the effects of social integration on FD contracting services among migrant populations. METHODS: In total, 120,106 respondents from the 2018 China Migrants Dynamic Survey were included in this study. Two multivariate regression models were used to estimate the effect of social integration and other factors on FD contracting services among migrant populations. RESULTS: This study found that only 14.0% of the migrant populations had a FD. Multiple dimensions of social integration and some covariates were shown to be positively associated with FD contracting services, including average monthly household income, local medical insurance (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.29-1.39), employment status (OR = 0.86, 95% CI = 0.82-0.91), settlement intention (OR = 1.15, 95% CI = 1.09-1.22), received health education (OR = 4.88, 95% CI = 4.51-5.27), sex (OR = 1.16, 95% CI = 1.12-1.20), age (OR = 1.66, 95% CI = 1.51-1.82), marital status (OR = 1.38, 95% CI = 1.31-1.46), sickness within a year (OR = 0.84, 95% CI = 0.79-0.89), and flow range (OR = 1.12, 95% CI = 1.07-1.16). CONCLUSIONS: All dimensions of social integration, including economic integration, social identity, and social involvement, are associated with FD contracting services among migrant populations. Policymakers should focus on improving the signing rates of migrant populations and implement more effective measures to enhance their social integration, such as settlement incentives and encouraging social participation.

Synthesis of gallic acid amide derivatives containing 1,3,4-thiadiazole and their inhibitory activity on Vibrio harveyi.

Using Gallic acid as raw material, 1-(substituted aromatic acyl)-4-(3,4,5-trihydroxybenzoyl) thiosemicarbazone was prepared by a two-step reaction and a series of brand-new gallic acid amide derivatives that contained 1,3,4-thiadiazole were synthesized by cyclic reaction. The newly prepared compounds' Vibrio harveyi inhibition activities were evaluated. The results indicated that all compounds showed different degree of inhibitory activity on Vibrio harveyi. Among them, the best inhibition effect was shown by compound 5b and its minimum inhibitory concentration (MIC) was 0.0313mg/mL.

Comparative efficacy and safety of immunotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma: a systematic review and network Meta-analysis.

BACKGROUND: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). METHODS: We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events. RESULTS: Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (probability, 61%) and PFS (probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (probability, 37%) and PFS (probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively. CONCLUSIONS: This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC. TRIAL REGISTRATION: PROSPERO registration number: (CRD 42021261554).

Evaluate the diagnostic and prognostic value of NUSAP1 in papillary thyroid carcinoma and identify the relationship with genes, proteins, and immune factors.

BACKGROUND: Nucleolar spindle-associated protein 1 (NUSAP1) is reported to be a useful diagnostic and prognostic marker for a variety of cancers, but relevant studies are lacking in papillary thyroid carcinoma (PTC). METHODS: The relationship between NUSAP1 expression and the overall survival (OS) of pan-cancer was examined by GEPIA and KMplot. We explored the relationship between NUSAP1 and clinical PTC data based on the THCA dataset of TCGA and the GEO dataset of NCBI; GO, KEGG analysis, and ceRNA networks were performed on co-expressed genes through LinkedOmics and Starbase. We assessed the relevance between NUSAP1 and the tumor microenvironment using ESTIMATE, correlations between NUSAP1 and immune cells with TIMER, the relationship between NUSAP1 and immunotherapy by TCIA, and small-molecule drugs targeting NUSAP1 that can be discovered using the CMap database. RESULTS: Higher expression of NUSAP1 in pan-cancer tissues was correlated with shorter OS. NUSAP1 was also significantly expressed in PTC tissues and was an independent prognostic risk factor. Compared to the NUSAP1 low expression group, the NUSAP1 high expression group was more likely to also have lymph node metastasis, pathological PTC type, shorter progression-free survival (PFS), and higher scores for immune checkpoint inhibitor treatment. The genes associated with NUSAP1 were mostly involved in the cell cycle, immune-related pathways, and AITD. Ten lncRNAs (GAS5, SNHG7, UCA1, SNHG1, HCP5, DLEU2, HOTAIR, TP53TG1, SNHG12, C9orf106), eleven miRNAs (hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-18a-5p, hsa-miR-18b-5p, hsa-miR-128-3p, hsa-miR-214-3p, hsa-miR-219a-2-3p, hsa-miR-339-5p, hsa-miR-494-3p, hsa-miR-545-3p, hsa-miR-769-5p), and one mRNA (NUSAP1) were constructed. NUSAP1 participated in the formation of the tumor microenvironment. CMap predicted the 10 most important small molecules about NUSAP1. CONCLUSIONS: In PTC, NUSAP1 shows good diagnostic value and prognostic value; NUSAP1 impacts the cell cycle, immune-related pathways, and AITD and has a complex effect on the tumor microenvironment in PTC.

Controls for multi-temporal patterns of riverine nitrogen and phosphorus export to lake: Implications for catchment management by high-frequency observations.

Intensifying human activity coupled with climate change increase the transport of excess riverine nitrogen (N) and phosphorus (P) loading from catchment to lake, leading to eutrophication and harmful algal blooms worldwide. To improve understanding of multi-temporal patterns of riverine N and P export and their hydro-biogeochemical controls over both episodic events and long-term trend, we analyzed and interpreted high-frequency data of total nitrogen (TN), ammonia-nitrogen (NH4-N), and total phosphorus (TP) provided by an automatic water quality monitoring station in a typical agricultural catchment draining to Lake Chaohu, China. Mann-Kendall test revealed a significant decreasing trend of riverine N and P concentration most of the time during 2018-2020. At the sub-daily scale, intraday TN concentrations varied by more than 1 mg/L in 31.8% of the period. Monthly TN and TP concentrations were particularly high in December 2019, indicating combined effect of hydrologic (long dry antecedent period and subsequent intensive rainfall events) and anthropogenic controls (fertilization and agricultural drainage). Significantly higher TN concentrations in winter and TP concentrations in summer reflected coupled dominances of precipitation and temperature on hydrologic and biogeochemical processes. Rainfall events with very heavy intensity drove disproportionate N and P loads (more than 20% of the total export) in only 3.2% of the period. Moderate and very heavy events registered the highest TN and TP concentrations, respectively. Our results highlighted the importance of automatic water quality monitoring station to reveal dynamics of riverine N and P export, which may imply future nutrient loading abatement plans for lake-connected catchment.

Molecular mechanism of modulating miR482b level in tomato with botrytis cinerea infection.

BACKGROUND: Plant miRNAs are involved in the response to biotic and abiotic stresses by altering their expression levels, and they play an important role in the regulation of plant resistance to stress. However, the molecular mechanism that regulates the expression levels of miRNAs in plants with biotic and abiotic stress still needs to be explored. Previously, we found that the expression of the miR482 family was changed in tomato infected by Botrytis cinerea. In this study, we investigated and uncovered the mechanism underlying the response of miR482 to B. cinerea infection in tomato. RESULTS: First, RT-qPCR was employed to detect the expression patterns of miR482b in tomato infected by B. cinerea, and results showed that miR482b primary transcripts (pri-miR482b) were up-regulated in B. cinerea-infected leaves, but the mature miR482b was down-regulated. Subsequently, we used rapid amplification cDNA end method to amplify the full-length of pri-miR482b. Result showed that the pri-miR482b had two isoforms, with the longer one (consisting 300 bp) having an extra fragment of 53 bp in the 3'-end compared with the shorter one. In vitro Dicer assay indicated that the longer isoform pri-miR482b-x1 had higher efficiency in the post-transcriptional splicing of miRNA than the shorter isoform pri-miR482b-x2. In addition, the transcription level of mature miR482b was much higher in transgenic Arabidopsis overexpressing pri-miR482b-x1 than that in OE pri-miR482b-x2 Arabidopsis. These results confirmed that this extra 53 bp in pri-miR482b-x1 might play a key role in the miR482b biogenesis of post-transcription processing. CONCLUSIONS: Extra 53 bp in pri-miR482b-x1 enhanced miR482b biogenesis, which elevated the transcription level of miR482b. This study clarified the response of miR482 to B. cinerea infection in tomato, thereby helping us further understand the molecular mechanisms that regulate the expression levels of other miRNAs.

MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway.

BACKGROUND: Mounting evidences have displayed that the dysregulation of miRNAs plays important roles in the pathogenesis of gastric cancer (GC). The purpose of this study was to explore the biological functions and potential mechanism of miR-489 in GC progression. METHODS: Quantitative real-time PCR (qRT-PCR) and western blot were performed to examine the mRNA expression and protein levels of miR-489 and HDAC7. The relationship between miR-489 and HDAC7 was analyzed by Spearman rank correlation. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays were conducted for determining the effect of miR-489 and HDAC7 on GC cell viability, migration, and invasion. TargetScan and luciferase reporter assay were used to confirm the target gene of miR-489 in GC cells. RESULTS: The findings showed that miR-489 was dramatically decreased in GC tissues and GC cell lines (SGC-7901 and MKN45). Moreover, it was closely correlated with overall survival (OS) and progression-free survival (PFS) of GC patients. Downregulation of miR-489 significantly promoted GC cell proliferation, invasion, and migration. Additionally, HDAC7 was confirmed as the direct target of miR-489. Knockdown of HDAC7 exerted inhibited effect on GC progression and it markedly overturned miR-489 inhibitor-medicated effect on GC cells. More interestingly, via targeting HDAC7, miR-489 blocked the activation of PI3K/AKT pathway in GC cells. CONCLUSIONS: Correctively, miR-489 played as a tumor suppressor in GC cell growth by targeting HDAC7, and miR-489 might function as a novel biomarker for diagnosis or therapeutic targets of human GC.

Effect of deletion of SUMOylation on dendritic cell function in septic mice and its role in sepsis. / SUMOåŒ–ç¼ºå¤±å¯¹è„“æ¯’ç—‡å°é¼ æ ‘çªçŠ¶ç»†èƒžåŠŸèƒ½çš„å½±å“åŠå ¶åœ¨è„“æ¯’ç—‡ä¸­çš„ä½œç”¨.

OBJECTIVES: To investigate the effect of deletion of small ubiquitin-like modifier (SUMO) on the function of dendritic cells (DC) in septic mice and its role in sepsis. METHODS: Septic models of DC-specific ubiquitin-conjugating enzyme 9 (UBC9) deficient (UBC9ΔDC) mice and wild type (WT) mice with cecal ligation and puncture (CLP) were established. The differences in 7-day mortality of the mice were analyzed. Bacteria loads of blood, liver, and spleen were tested. ELISA was used to detect the levels of IL-1ß, IL-6, IL-18, and TNF-α in plasma and culture medium of bone marrow-derived dendritic cells (BMDC). The levels of cytokine IFN-γ and IL-4 in supernatant of spleen mononuclear cells were detected by ELISA.The expressions of MHC II, CD54, and CD80 on the cell surface of DC were analyzed by flow cytometry. The percentages of Th1, and Th2 cells in spleen mononuclear cells were analyzed by flow cytometry. RESULTS: Compared with the WT septic mice, the 7-day mortality of UBC9ΔDC septic mice was higher (P<0.05). Bacterial loads in blood (P<0.01), liver (P<0.01), and spleen (P<0.05) were significantly increased in UBC9ΔDC septic mice. Levels of IL-1ß and IL-18 in plasma and culture supernatant of BMDC were also significantly increased in UBC9ΔDC septic mice (all P<0.01). There was no significant difference in the number of DC and the expression of cell surface molecules in DC of UBC9ΔDC septic mice (all P>0.05).The percentage of Th2 cells was significantly increased in UBC9ΔDC septic mice (P<0.05). The ratio of Th1 to Th2 was decreased in UBC9ΔDC septic mice but the difference was not significant (P>0.05). Levels of IFN-γ and IL-4 were increased in UBC9ΔDC septic mice, and the ratio of IFN-γ to IL-4 were significantly decreased in UBC9ΔDC septic mice (all P<0.05). CONCLUSIONS: Deletion of SUMOylation may increase the mortality of mice with sepsis through regulating the release of inflammatory factors from DC and abnormal activation of T cells by DC.

Interleukin-12 receptor ß2 from grass carp: Molecular characterization and its involvement in Aeromonas hydrophila-induced intestinal inflammation.

Interleukin-12 receptor ß2 (IL-12Rß2) is a signaling subunit of heterodimeric receptors for IL-12 and IL-35. It plays important regulatory functions in the development of Th1 cells and in the expression of inflammatory cytokines in mammals and other higher vertebrates. However, little is known about IL-12Rß2 in teleost fish. In this work, we have cloned and characterized IL-12Rß2 from grass carp (Ctenopharyngodon idella). The full-length cDNA of grass carp IL-12Rß2 is 2875 bp, which encodes a mature protein with 741 amino acids. This mature protein contains three fibronectin type III domains, a transmembrane helix, and CXW and WSXWS-like motifs that are characteristic of the type I cytokine receptor family. Phylogenetic analysis revealed that cyprinid fish IL-12Rß2 formed a single branch, clearly separated from those of other vertebrates. We expressed and purified a recombinant grass carp IL-12Rß2 protein containing major antigenic regions, which was used to raise a polyclonal antibody. The specificity of the antibody was assessed by Western blotting analysis of whole cell lysates from Escherichia coli cells expressing the recombinant IL-12Rß2, grass carp intestinal intraepithelial lymphocytes, and cultured C. idella kidney cells. To explore the potential regulatory role of IL-12Rß2 in inflammation, we generated an intestinal inflammation model by anal intubation of fish with Aeromonas hydrophila. Immunohistochemical staining of the inflamed intestines revealed that IL-12Rß2 expression is consistent with inflammatory cell recruitment during intestinal inflammation. Real-time quantitative PCR revealed that IL-12Rß2 is widely expressed in normal tissues and is up-regulated in most tissues after infecting with A. hydrophila. We found that IL-12Rß2, IL-12p35, and interferon-γ were expressed in similar patterns in the intestines during inflammation. Taken together, our results suggest that IL-12Rß2 is involved in the regulation of intestinal inflammation.

Genome sequencing and characterization of three Bacillus cereus-specific phages, DK1, DK2, and DK3.

In the study, three Bacillus cereus-specific phages, named DK1, DK2 and DK3, belonging to the family Podoviridae, were isolated from Pearl River water and sludge in Guangzhou, China. The genomes of DK1, DK2 and DK3 were 27,180 bp, 26,357 bp, and 26,865 bp in length and contained 49, 45 and 46 open reading frames, respectively. Among the three phages, DK2 shared the highest genome sequence similarity (96% identity) with DK3. Genes encoding rRNA, tRNA, virulence factors and antibiotic resistance were absent in these phage genomes. In addition, comparative genomic and phylogenetic analysis revealed that they were novel phages of B. cereus. Each genome encoded a putative endolysin that might be of value for the control of the foodborne pathogen B. cereus.

Identification of 10 transcripts of FREP in penaeid shrimp Litopenaeus vannamei.

Fibrinogen-related proteins (FREPs) are widely distributed in vertebrates and invertebrates and known having Fibrinogen-related domains (FReDs) which function in multiple aspects, especially in innate immune response as pattern recognition receptors. However, there is no any report about FREP in penaeid shrimp Litopenaeus vannamei. Here, totally 10 transcripts of FREP were isolated and named LvFREP1.1, 1.2 until 1.10. All of the 10 transcripts have high identity in their 3' ends and encode conserved FReDs. Since the 10 transcripts are highly similar we could not design any primers that can amplify a single transcript. We chose a pair of primers corresponding to part of LvFREP1.1 and LvFREP1.5 to examine their expression. Tissue distribution indicated LvFREP1.1 and LvFREP1.5 mRNA locates in hemocytes, gills, intestine, hearts and slightly in nerve. The expression of LvFREP1.1 and LvFREP1.5 behaves differently post bacteria and virus infection. Besides, recombinant LvFReD could agglutinate bacteria Vibrio harveyi in the presence of Ca2+. These initial data presents the diversity of FREPs in penaeid shrimp and also push us to further explore their roles in shrimp immune response.

Didactical approaches and insights into environmental processes and cardiovascular hazards of arsenic contaminants.

Arsenic, as a metalloid, has the ability to move and transform in different environmental media. Its widespread contamination has become a significant environmental problem and public concern. Arsenic can jeopardize multiple organs through various pathways, influenced by environmental bioprocesses. This article provides a comprehensive overview of current research on the cardiovascular hazards of arsenic. A bibliometric analysis revealed that there are 376 papers published in 145 journals, involving 40 countries, 631 institutions, and 2093 authors, all focused on arsenic-related concerns regarding cardiovascular health. China and the U.S. have emerged as the central hubs of collaborative relationships and have the highest number of publications. Hypertension and atherosclerosis are the most extensively studied topics, with redox imbalance, apoptosis, and methylation being the primary mechanistic clues. Cardiovascular damage caused by arsenic includes arrhythmia, cardiac remodeling, vascular leakage, and abnormal angiogenesis. However, the current understanding is still inadequate over cardiovascular impairments, underlying mechanisms, and precautionary methods of arsenic, thus calling an urgent need for further studies to bridge the gap between environmental processes and arsenic hazards.

Tet1/DLL3/Notch1 signal pathway affects hippocampal neurogenesis and regulates depression-like behaviour in mice.

Ten-eleven translocation protein 1 (Tet1) is associated with the regulation of depression-like behaviour in mice. However, the mechanism by which Tet1 affects neurogenesis in mice to regulate depression-like behaviours remains unclear. In this study, the chronic social defeat stress (CSDS) paradigm was constructed by overexpressing Tet1 protein in the mouse hippocampus, and 5-ethynyl-2'-deoxyuridine (EdU, 50 mg/kg) was injected on the seventh day to explore the mechanism of the regulation of the Tet1/Delta-like protein 3 (DLL3)/Notch1 protein pathway in mice hippocampal neurogenesis and its influence on depression-like behaviour. Following CSDS, the expression level of Tet1 decreased significantly. Moreover, due to the downregulation of Tet1 protein, the maintenance of the DNA methylation and demethylation balance was affected, resulting in a significant increase in the methylation levels of Notch1 and DLL3 and a significant decrease in the protein expression levels of DLL3, Notch1, and brain-derived neurotrophic factor (BDNF). At the same time, the proliferation and differentiation of neurones were affected, which was related to a significant decrease in the number of EdU+, doublecortin (DCX)+, and Ki67+ cells in the hippocampus of the CSDS model mice. When the Tet1 protein was overexpressed in the mouse hippocampus, DLL3 and Notch1 protein expression levels were upregulated, promoting hippocampal neurogenesis and alleviating depression-like behaviour in mice. These findings suggest that regulation of the hippocampal Tet1/DLL3/Notch1 protein pathway to influence neurogenesis may be a therapeutic strategy for depression.

Whether medicine supply is really meeting primary health care needs: a mixed-methods study in Shandong Province, China.

BACKGROUND: With the aging population, the increasing prevalence of chronic non-communicable diseases, and the diversified needs for primary health care (PHC) medicines, it is necessary to rethink the functional role of the supply of PHC medicines. This study aims to evaluate the supply of PHC medicines and the status of meeting PHC medicine needs. METHODS: The mixed-methods study was conducted to evaluate the supply of PHC medicines in Shandong Province. In the quantitative study, survey questionnaires were distributed to county hospitals, township hospitals, and patients, and a prescription review was performed in township hospitals. In the qualitative study, semi-structured interviews were conducted with the pharmacy managers, physicians, and patients in county hospitals, township hospitals, and village clinics. A senior pharmacist from a tertiary hospital who has rich experience on the indications for medicine use, accompanied us on a visit to inspect the PHC pharmacies to survey medicine equipment with a professional perspective. RESULTS: Quantitative analysis revealed that 211 county hospitals and 1,581 township hospitals participated in the survey, revealing the median annual frequency of medicine shortages of 5.0 times for county hospitals and 2.0 times for township hospitals. Of the 6,323 patient medication surveys, after excluding 152 patients not involved in medication use, 945 (15.3%) indicated medicine shortages, with half of these attributable to institutions lacking required medicines (52.8%). On average, the prescription qualified rate of 37 township hospitals was 72.2%. Four final themes emerged during the qualitative data analysis: (1) Supply of PHC medicines; (2) Solutions to the shortage of off-list medicines; (3) Appropriateness of PHC medicines list; (4) Pharmacist workforce development and pharmacy services. CONCLUSIONS: The discrepancy between patients' need for PHC medicine and present medicine supply is noteworthy. It is suggested that governments should optimize the existing lists to adequately meet patient medicine needs and prioritize medicines for chronic diseases, which is also particularly important for developing countries. Integrated health care may be a novel strategy to establish unified medicines list and achieve uniform pharmaceutical services in PHC.