Loss of cilia in chemosensory neurons inhibits pathogen avoidance in Caenorhabditis elegans.

Pathogen avoidance is a crucial and evolutionarily conserved behavior that enhances survival by preventing infection in diverse species, including Caenorhabditis elegans (C. elegans). This behavior relies on multiple chemosensory neurons equipped with cilia that are exposed to the external environment. However, the specific role of neuronal cilia in pathogen avoidance has not been completely elucidated. Herein, we discovered that osm-3(p802) mutants, which lack chemosensory neuronal cilia, exhibit slower avoidance of the pathogen Pseudomonas aeruginosa PA14, but not Escherichia coli OP50. This observation was consistent when osm-3(p802) mutants were exposed to P. aeruginosa PAO1. Following an encounter with PA14, the pumping, thrashing, and defecation behaviors of osm-3 mutants were comparable to those of the wild-type. However, the osm-3 mutants demonstrated reduced intestinal colonization of PA14, suggesting that they have stronger intestinal clearance ability. We conducted RNA-seq to identify genes responding to external stimuli that were differentially expressed owing to the loss of osm-3 and PA14 infection. Using RNAi, we demonstrated that three of these genes were essential for normal pathogen avoidance. In conclusion, our findings demonstrate that the loss of chemosensory neuronal cilia reduces pathogen avoidance in C. elegans while delaying intestinal colonization.

Global trends and research hotspots of PCSK9 and cardiovascular disease: a bibliometric and visual analysis.

Background: Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently, considerable focus has been directed towards the prevention and management of CVD. PCSK9, a frequently targeted element in the treatment and prevention of CVD, can reduce cardiovascular risk by effectively lowering lipid levels even in the context of statin therapy. It also exhibits substantial potential in the diagnosis and treatment of familial hypercholesterolemia from genetic aspects. This bibliometric study aims to analyze and visualize the global trends and emerging hotspots of PCSK9 and CVD researches and provide researchers with new perspectives in further studies. Methods: The data was obtained from the Web of Science Core Collection database. A total of 2,474 publications related to PCSK9 and CVD published between January 2006 and July 2023 were included. The VOSviewer was used to analyze most-cited references, co-authorship, co-citation, co-occurrence and generate a collaborative network map of authors, countries, and institutions. CiteSpace was used to analyze author and institution centroids, keyword bursts, and timeline graphs. Result: A total of 2,474 articles related to CVD and PCSK9 were included. The number of articles and citations show an increasing trend from year to year. Publications were mainly from the United States. The most active institution was Amgen Inc. Watts, Gerald F. was the most prolific author. Atherosclerosis was the most published journal. Literature co-citation and keyword co-occurrence revealed that early studies focused on the lipid-lowering effects of PCSK9 inhibitors in the context of statins therapy, long-term efficacy, adverse effects, LDLR, diagnosis and treatment of familial hypercholesterolemia. In recent years, myocardial ischemic protection, CRISPR-based editing, and new therapeutic strategies for arteriosclerotic cardiovascular disease have gotten wide attention. The protein convertase, inflammation, beta-polyacetate, and inclisiran may be the important future research directions. Conclusion: This study analyses the current status and global trends in the CVD and PCSK9 studies comprehensively, which may provide researchers and policymakers with new and comprehensive perspectives on in this field of research.

Temporal turnover of viral biodiversity and functional potential in intertidal wetlands.

As the central members of the microbiome networks, viruses regulate the composition of microbial communities and drive the nutrient cycles of ecosystems by lysing host cells. Therefore, uncovering the dynamic patterns and the underlying ecological mechanisms mediating the tiniest viral communities across space and through time in natural ecosystems is of crucial importance for better understanding the complex microbial world. Here, the temporal dynamics of intertidal viral communities were investigated via a time-series sampling effort. A total of 1911 viral operational taxonomic units were recovered from 36 bimonthly collected shotgun metagenomes. Functionally important auxiliary metabolic genes involved in carbohydrate, sulfur, and phosphorus metabolism were detected, some of which (e.g., cysH gene) were stably present within viral genomes over time. Over the sampling period, strong and comparable temporal turnovers were observed for intertidal viromes and their host microbes. Winter was determined as the pivotal point for the shifts in viral diversity patterns. Notably, the viral micro-diversity covaried with the macro-diversity, following similar temporal patterns. The relative abundances of viral taxa also covaried with their host prokaryotes. Meanwhile, the virus-host relationships at the whole community level were relatively stable. Further statistical analyses demonstrated that the dynamic patterns of viral communities were highly deterministic, for which temperature was the major driver. This study provided valuable mechanistic insights into the temporal turnover of viral communities in complex ecosystems such as intertidal wetlands.

Effect of turbulence-induced sediment resuspension and sedimentation on underwater wireless optical communication.

In real-life marine environments, the composition and grain size of suspended sediments and the resuspension and sedimentation of sediments caused by turbulence may have a significant impact on underwater wireless optical communication (UWOC). However, to date, researchers have not conducted quantitative research on this issue. To this end, we innovatively study the effects of different compositions and grain sizes of suspended sediments on UWOC and the effects of turbulence-induced sediment resuspension and sedimentation on UWOC in this paper. Quartz and kaolin with different grain sizes are used to simulate sediments in seawater. An oscillating grid that can vary frequency and stroke is used to generate turbulence of different intensities. By comparing the turbidity and optical power density of different simulated sediments with different grain sizes, we find that the smaller the grain size of the simulated sediments, the higher the bit error rate (BER) under the same turbidity. But different simulated sediments with different grain sizes have similar effects on BER performance under the same optical power density. Therefore, turbidity can be used to characterize the changes of underwater channels, and optical power density can be used to evaluate the attenuation of light at the receiving end after transmission through the underwater channel. By continuously changing the frequency of the grid to cause the sediments to resuspend and sink, we prove that the process of turbulence-induced sediment resuspension and sedimentation can seriously affect the BER performance. The larger the frequency of the grid, the greater the turbulence intensity and the worse the BER performance. This study lays a foundation for the practical application of UWOC in mobile ocean observation networks.

A pattern for the early, middle, and late phase of tea chrysanthemum response to Fusarium oxysporum.

Chrysanthemum morifolium is cultivated worldwide and has high ornamental, tea, and medicinal value. With the increasing area of chrysanthemum cultivation and years of continuous cropping, Fusarium wilt disease frequently occurs in various production areas, seriously affecting the quality and yield and causing huge economic losses. However, the molecular response mechanism of Fusarium wilt infection remains unclear, which limits the molecular breeding process for disease resistance in chrysanthemums. In the present study, we analyzed the molecular response mechanisms of 'Huangju,' one of the tea chrysanthemum cultivars severely infested with Fusarium wilt in the field at the early, middle, and late phases of F. oxysporum infestation. 'Huangju' responded to the infestation mainly through galactose metabolism, plant-pathogen interaction, auxin, abscisic acid, and ethylene signalling in the early phase; galactose metabolism, plant-pathogen interaction, auxin, salicylic acid signal, and certain transcription factors (e.g., CmWRKY48) in the middle phase; and galactose metabolism in the late phase. Notably, the galactose metabolism was important in the early, middle, and late phases of 'Huangju' response to F. oxysporum. Meanwhile, the phytohormone auxin was involved in the early and middle responses. Furthermore, silencing of CmWRKY48 in 'Huangju' resulted in resistance to F. oxysporum. Our results revealed a new molecular pattern for chrysanthemum in response to Fusarium wilt in the early, middle, and late phases, providing a foundation for the molecular breeding of chrysanthemum for disease resistance.

Identification and characterization of long non-coding RNAs in mammary gland tissues of Chinese Holstein cows.

LncRNAs (Long non-coding RNA) is an RNA molecule with a length of more than 200 bp. LncRNAs can directly act on mRNA, thus affecting the expression of downstream target genes and proteins, and widely participate in many important physiological and pathological regulation processes of the body. In this study, RNA-Seq was performed to detect lncRNAs from mammary gland tissues of three Chinese Holstein cows, including three cows at 7 d before calving and the same three cows at 30 d postpartum (early lactation stage). A total of 1,905 novel lncRNAs were detected, 57.3% of the predicted lncRNAs are ≥ 500 bp and 612 lncRNAs are intronic lncRNAs. The exon number of lncRNAs ranged from 2 to 10. A total of 96 lncRNAs were significantly differentially expressed between two stages, of which 47 were upregulated and 49 were downregulated. Pathway analysis found that target genes were mainly concentrated on the ECM-receptor interaction, Jak-STAT signaling pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway. This study revealed the expression profile and characteristics of lncRNAs in the mammary gland tissues of Holstein cows at non-lactation and early lactation periods, and provided a basis for studying the functions of lncRNAs in Holstein cows during different lactation periods.

The mammary gland of dairy cows is the main place of milk synthesis and secretion, and plays a vital role in the process of milk production. LncRNAs (Long non-coding RNAs) are a class of non-coding RNAs with a length greater than 200 bp and do not encode protein, which can regulate gene expression at the transcriptional, post-transcriptional and chromatin levels, with biological functions such as regulating cell proliferation, differentiation, and apoptosis. Relevant studies in humans and model animals have shown that lncRNAs participate in mammalian mammary gland development and lactation, but there are few studies on lncRNAs regulation of mammary gland development and lactation in dairy cows. Therefore, this study aims to reveal the potential role of lncRNAs in the mammary gland of dairy cows through screening, identification, and functional research of differentially expressed lncRNAs at different periods of mammary gland development (pregnancy and early lactation period). It provides a reference for the follow-up study on the regulatory mechanism of dairy cows' mammary gland health.

Identification of immunogenic cell death-related damage-related molecular patterns (DAMPs) to predict outcomes in patients with head and neck squamous cell carcinoma.

PURPOSE: Head and neck cancer is the sixth most common type of cancer worldwide, wherein the immune responses are closely associated with disease occurrence, development, and prognosis. Investigation of the role of immunogenic cell death-related genes (ICDGs) in adaptive immune response activation may provide cues into the mechanism underlying the outcome of HNSCC immunotherapy. METHODS: ICDGs expression patterns in HNSCC were analyzed, after which consensus clustering in HNSCC cohort conducted. A 4-gene prognostic model was constructed through LASSO and Cox regression analyses to analyze the prognostic index using the TCGA dataset, followed by validation with two GEO datasets. The distribution of immune cells and the response to immunotherapy were compared between different risk subtypes through multiple algorithms. Moreover, immunohistochemical (IHC) analyses were conducted to validate the prognostic value of HSP90AA1 as a predictor of HNSCC patient prognosis. In vitro assays were performed to further detect the effect of HSP90AA1 in the development of HNSCC. RESULTS: A novel prognostic index based on four ICDGs was constructed and proved to be useful as an independent factor of HNSCC prognosis. The risk score derived from this model grouped patients into high- and low-risk subtypes, wherein the high-risk subtype had worse survival outcomes and poorer immunotherapy response. IHC analysis validated the applicability of HSP90AA1 as a predictor of prognosis of HNSCC patients. HSP90AA1 expression in tumor cells promotes the progression of HNSCC. CONCLUSIONS: Together, these results highlight a novel four-gene prognostic signature as a valuable tool to assess survival status and prognosis of HNSCC patients.

Advances in regenerated cellulosic aerogel from waste cotton textile for emerging multidimensional applications.

Rapid development of society and the improvement of people's living standards have stimulated people's keen interest in fashion clothing. This trend has led to the acceleration of new product innovation and the shortening of the lifespan for cotton fabrics, which has resulting in the accumulation of waste cotton textiles. Although cotton fibers can be degraded naturally, direct disposal not only causes a serious resource waste, but also brings serious environmental problems. Hence, it is significant to explore a cleaner and greener waste textile treatment method in the context of green and sustainable development. To realize the high-value utilization of cellulose II aerogel derived from waste cotton products, great efforts have been made and considerable progress has been achieved in the past few decades. However, few reviews systematically summarize the research progress and future challenges of preparing high-value-added regenerated cellulose aerogels via dissolving cotton and other cellulose wastes. Therefore, this article reviews the regenerated cellulose aerogels obtained through solvent methods, summarizes their structure, preparation strategies and application, aimed to promote the development of the waste textile industry and contributed to the realization of carbon neutrality.

Protocol for survival assay of Caenorhabditis elegans to Pseudomonas aeruginosa PA14 infection.

The nematode Caenorhabditis elegans is a powerful model organism for studying the molecular and cellular mechanisms of innate immunity governed by the intestine. Here, we present a protocol to perform C. elegans survival assays to infection by the bacterial pathogen Pseudomonas aeruginosa PA14. Specifically, we describe steps for preparing C. elegans strains and PA14 bacteria for survival assays. This protocol will assist researchers to study genes involved in intestinal innate immunity and gut defense against pathogen infection. For complete details on the use and execution of this protocol, please refer to Liu et al.1 and Zheng et al.2.

Development and evaluation of time-resolved rapid immunofluorescence test for detection of TSOL18 specific antibody in porcine cysticercosis infections.

BACKGROUND: Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. RESULTS: ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen's κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃. CONCLUSIONS: In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.

The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study.

OBJECTIVES: Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. METHODS: Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. RESULTS: The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03-1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. DISCUSSION: This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.

Ultrasensitive Detection of Prostate Specific Antigen by an Unlabeled Fluorescence Aptasensor Based on the AIE Effect.

The accurate and sensitive detection of prostate specific antigen (PSA) is vital for the early diagnosis and treatment of prostate cancer. To this end, an unlabeled fluorescent aptasensor was constructed by using a novel Compound B {1,1'-(1,4-phenylene) bis(3-ethyl-1H-imidazol-3-ium) iodide} with aggregation-induced emission (AIE) activity as a fluorescence signal and NH2-Fe3O4 particle as an adsorption platform. Compound B could combine with prostate specific antigen aptamers (PSA-Apt) to form a PSA-Apt/B complex, which further generated the AIE effect. Then, PSA was added to the PSA-Apt/B solution. PSA combined with PSA-Apt/B to form the PSA-Apt/B/PSA complex. Next, NH2-Fe3O4 magnetic particles were added to the solution. Given that PSA-Apt/B/PSA would no longer combine with NH2-Fe3O4 magnetic particles, the PSA-Apt/B/PSA complex remained in the supernate after magnet separation, and the supernate showed strong fluorescence (I). When no PSA was added to the PSA-Apt/B solution, PSA-Apt/B could combine with NH2-Fe3O4 magnetic particles and would be sucked into the bottom of the test tube by magnet, and the supernate would show weak fluorescence (I0). Result showed that the difference between the above-mentioned two fluorescence values (∆I = I - I0) had an excellent linear relationship with the PSA concentration within the concentration range of 0.01-10 ng/mL, and its limit of detection was 3 pg/mL (S/N = 3). In addition, the sensor has high accuracy and can be directly used to test PSA in actual serum samples.

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation.

Significance: Pulsed infrared neural stimulation (INS, 1875 nm) is an emerging neurostimulation technology that delivers focal pulsed heat to activate functionally specific mesoscale networks and holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in cerebral cortex. Aim: Estimates of summed population neuronal response time courses provide a potential basis for neural and hemodynamic signals described in other studies. Approach: Using two-photon calcium imaging in mouse somatosensory cortex, we have examined the effect of INS pulse train application on hSyn neurons and mDlx neurons tagged with GCaMP6s. Results: We find that, in anesthetized mice, each INS pulse train reliably induces robust response in hSyn neurons exhibiting positive going responses. Surprisingly, mDlx neurons exhibit negative going responses. Quantification using the index of correlation illustrates responses are reproducible, intensity-dependent, and focal. Also, a contralateral activation is observed when INS applied. Conclusions: In sum, the population of neurons stimulated by INS includes both hSyn and mDlx neurons; within a range of stimulation intensities, this leads to overall excitation in the stimulated population, leading to the previously observed activations at distant post-synaptic sites.

The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses.

AIMS: The causal relationship between sarcopenia-related traits and ischemic stroke (IS) remains poorly understood. This study aimed to explore the causal impact of sarcopenia-related traits on IS and to identify key mediators of this association. METHODS: We conducted univariable, multivariable two-sample, and two-step Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. This included data for appendicular lean mass (ALM), hand grip strength (HGS), and usual walking pace (UWP) from the UK Biobank, and IS data from the MEGASTROKE consortium. Additionally, 21 candidate mediators were analyzed based on their respective GWAS data sets. RESULTS: Each 1-SD increase in genetically proxied ALM was associated with a 7.5% reduction in the risk of IS (95% CI: 0.879-0.974), and this correlation remained after controlling for levels of physical activity and adiposity-related indices. Two-step MR identified that six mediators partially mediated the protective effect of higher ALM on IS, with the most significant being coronary heart disease (CHD, mediating proportion: 39.94%), followed by systolic blood pressure (36.51%), hypertension (23.87%), diastolic blood pressure (15.39%), type-2 diabetes mellitus (T2DM, 12.71%), and low-density lipoprotein cholesterol (7.97%). CONCLUSION: Our study revealed a causal protective effect of higher ALM on IS, independent of physical activity and adiposity-related indices. Moreover, we found that higher ALM could reduce susceptibility to IS partially by lowering the risk of vascular risk factors, including CHD, hypertension, T2DM, and hyperlipidemia. In brief, we elucidated another modifiable factor for IS and implied that maintaining sufficient muscle mass may reduce the risk of such disease.

In-Situ Self-Assembly Dipole Shielding Layer Toward Efficient and Stable Inorganic Perovskite Solar Cells.

Despite CsPbI2.75Br0.25 inorganic perovskites exhibit high potential for single-junction and/or tandem solar cells, unexpected non-radiative recombination, and mismatched interfacial band alignment within the inorganic perovskite solar cells (PSCs) disadvantageously affect their photovoltaic performance. Rational design of the dipole shielding layer (DSL) is vital to realize a win-win situation for the defect passivation and band alignment. Herein, A-site dipole molecules, that is, neopentylamine and 2-methylbutylamine, are employed for in-situ self-assembly of a thus-far unreported DSL at the interface between 3D perovskite and hole transport layer. The as-prepared DSL demonstrates a 2D RP phase perovskite and the lattice-matching structurally-stable DSL@3D perovskite enables to alleviate the unexpected surface defects and suppress the spontaneous non-radiative recombination by means of effectively tuning the surface work function via regulating the dipole moment length and Van der Waals gap. Accordingly, the top dipole-modified inorganic PSCs exhibit a champion power conversion efficiency (PSC) as high as 19.77% and a fill factor over 83%. Equally importantly, the corresponding solar cells demonstrate a remarkable enhanced stability, maintaining 90% of its initial efficiency for more than 1200 h without encapsulation under a 20% ± 5% relative humidity.

Neutrophil extracellular traps promote invasion and metastasis via NLRP3-mediated oral squamous cell carcinoma pyroptosis inhibition.

Neutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC.

FADD promotes type I interferon production to suppress porcine reproductive and respiratory syndrome virus infection.

Porcine reproductive and respiratory syndrome (PRRS) is an epidemic animal infectious disease worldwide, causing huge economic losses to the global swine industry. Fas-associated death domain (FADD) was previously reported to be an adaptor protein that functions in transferring the apoptotic signals regulated by the death receptors. In the current study, we unravel its unidentified role in promoting type I interferon (IFN) production during PRRS virus (PRRSV) infection. We identified that FADD inhibited PRRSV infection via promotion of type I IFN transcription. Overexpression of FADD suppressed the replication of PRRSV, while knockout of FADD increased viral titer and nucleocapsid protein expression. Mechanistically, FADD promoted mitochondrial antiviral signaling protein (MAVS)-mediated production of IFN-ß and some IFN-stimulated genes (ISGs). Furthermore, FADD exerted anti-PRRSV effects in a MAVS-dependent manner and increased the type I IFN signaling during PRRSV infection. This study highlights the importance of FADD in PRRSV replication, which may have implications for the future control of PRRS.

Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells. We discovered that direct coupling of CD40 ligand and CD40 receptor constituted the key signaling pathway governing lanosterol biosynthesis, and disruption of CD40/CD40L interaction using an anti-CD40 neutralizing antibody or conditional depletion of Cd40l in BMSCs successfully eliminated the iron level and lanosterol production of MM cells localized in the Vk*MYC Vk12653 or NSG mouse models. Our study deciphers the mechanism of BMSCs dictating ferroptosis of MM cells and highlights the therapeutic potential of non-apoptosis strategies for managing refractory or relapsed MM patients.

Evaluation of probiotics in the treatment of hypothyroidism in early pregnancy combined with small intestinal bacterial overgrowth.

The aim of this study was to investigate the association between hypothyroidism in early pregnancy and small intestinal bacterial overgrowth (SIBO) and the effect of probiotics. Patients with hypothyroidism in early pregnancy and normal pregnant women during the same period were included in the methane-hydrogen breath test to compare the incidence of SIBO, smoothed curve fit, and differences in clinical symptoms. For those who combined with SIBO, the rate of clinical symptom conversion, thyroid hormones, and changes in associated inflammatory indexes were compared after 21 days of treatment with probiotics on top of conventional levothyroxine sodium tablets. The results are as follows: (1) The incidence of combined SIBO in patients with hypothyroidism in pregnancy was 56.0%, significantly higher than the 28.0% of normal pregnant women during the same period. (2) The highest value of hydrogen plus methane gas in 90 min in pregnancy hypothyroid patients showed a significant negative correlation with FT4 (p < .001, SD = 0.169). (3) Abdominal distension symptoms were significantly increased in both groups after combined SIBO (p = .036, p = .025), and the conversion rate after treatment was 69.2% and 75.0%, respectively. (4) In hypothyroidism, pregnancy combined with SIBO, TSH, and CRP was higher before treatment (p = .001, p = .012) and decreased significantly after treatment (p = .001, p = .008). Hypothyroidism in early pregnancy is associated with SIBO, and probiotic treatment is significantly effective.

CMYC-initiated HNF1A-AS1 overexpression maintains the stemness of gastric cancer cells.

Cancer stem cells (CSCs) are believed to be responsible for cancer metastasis and recurrence due to their self-renewal ability and resistance to treatment. However, the mechanisms that regulate the stemness of CSCs remain poorly understood. Recently, evidence has emerged suggesting that long non-coding RNAs (lncRNAs) play a crucial role in regulating cancer cell function in different types of malignancies, including gastric cancer (GC). However, the specific means by which lncRNAs regulate the function of gastric cancer stem cells (GCSCs) are yet to be fully understood. In this study, we investigated a lncRNA known as HNF1A-AS1, which is highly expressed in GCSC s and serves as a critical regulator of GCSC stemness and tumorigenesis. Our experiments, both in vitro and in vivo, demonstrated that HNF1A-AS1 maintained the stemness of GC cells. Further analysis revealed that HNF1A-AS1, transcriptionally activated by CMYC, functioned as a competing endogenous RNA by binding to miR-150-5p to upregulate ß-catenin expression. This in turn facilitated the entry of ß-catenin into the nucleus to activate the Wnt/ß-catenin pathway and promote CMYC expression, thereby forming a positive feedback loop that sustained the stemness of GCSCs. We also found that blocking the Wnt/ß-catenin pathway effectively inhibited the function of HNF1A-AS1, ultimately resulting in the inhibition of GCSC stemness. Taken together, our results demonstrated that HNF1A-AS1 is a regulator of the stemness of GCSCs and could serve as a potential marker for targeted GC therapy.