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Abstract Background The relationship between gut microbiota and vertigo, specifically Benign Paroxysmal Vertigo (BPV) and Vertigo of Central (VC), remains underexplored. Aim and hypotheses This study aims to investigate the causal relationships between gut microbiota and two types of vertigo, BPV and VC. Additionally, the study seeks to explore the mediation effects of metabolic, inflammatory, and psychological factors on these relationships. We hypothesize that specific taxa of gut microbiota have a causal effect on the risk of developing BPV and VC. The mediation effects of HbA1c, obesity, major depression, and interleukin-18 levels significantly influence the relationships between gut microbiota and vertigo. Method Utilizing a bidirectional two-sample Mendelian randomization approach, this study investigated causal associations between gut microbiota and the two types of vertigo. A network MR assessed mediation effects of HbA1c, major depression, obesity, and interleukin-18 levels, with data sourced from several consortia, including MiBioGen. Results Distinct gut microbiota displayed varying influences on BPV and VC risks. A total of ten taxa affect BPV. Among these, two taxa have an odds ratio (OR) greater than 1, including one class, one order. Conversely, eight taxa have an OR less than 1, encompassing four families, three genera, and one order. The OR for these taxa ranges from 0.693 to 0.930, with p-values between 0.006 and 0.048. For VC, eight taxa were found to have an impact. Five of these taxa exhibit an OR greater than 1, including four genera and one phylum. The OR for these taxa ranges from 1.229 to 2.179, with p-values from 0.000 to 0.046. The remaining three taxa have an OR less than 1, comprising one family and two genera, with an OR range of 0.445 to 0.792 and p-values ranging from 0.013 to 0.050. The mediation analysis for BPV shows that major depression, obesity, and HbA1c are key mediators between specific taxa and BPV. Major depression mediates 28.77% of the effect of family Rhodospirillaceae on BPV. Obesity mediates 13.90% of the effect of class Lentisphaeria/order Victivallales. HbA1c mediates 11.79% of the effect of genus Bifidobacterium, 11.36% of family Bifidobacteriaceae/order Bifidobacteriales. For VC, interleukin-18 levels and major depression are significant mediators. Interleukin-18 levels mediate 6.56% of the effect of phylum Actinobacteria. Major depression mediates 6.51% of the effect of genus Alloprevotella. Conclusion The study highlights potential causal links between gut microbiota and vertigo, emphasizing metabolic and psychological mediators. These insights underscore the therapeutic potential of targeting gut health in vertigo management.

Abstract Background RNA–DNA hybrids or R-loops are associated with deleterious genomic instability and protective immunoglobulin class switch recombination (CSR). However, the underlying phenomenon regulating the two contrasting functions of R-loops is unknown. Notably, the underlying mechanism that protects R-loops from classic RNase H-mediated digestion thereby promoting persistence of CSR-associated R-loops during CSR remains elusive. Results Here, we report that during CSR, R-loops formed at the immunoglobulin heavy (IgH) chain are modified by ribose 2′-O-methylation (2′-OMe). Moreover, we find that 2′-O-methyltransferase fibrillarin (FBL) interacts with activation-induced cytidine deaminase (AID) associated snoRNA aSNORD1C to facilitate the 2′-OMe. Moreover, deleting AID C-terminal tail impairs its association with aSNORD1C and FBL. Disrupting FBL, AID or aSNORD1C expression severely impairs 2′-OMe, R-loop stability and CSR. Surprisingly, FBL, AID’s interaction partner and aSNORD1C promoted AID targeting to the IgH locus. Conclusion Taken together, our results suggest that 2′-OMe stabilizes IgH-associated R-loops to enable productive CSR. These results would shed light on AID-mediated CSR and explain the mechanism of R-loop-associated genomic instability.

IntroductionShrimp is an important aquaculture species worldwide. Vibrio parahaemolyticus (VP) is an opportunistic pathogen of Litopenaeus vannamei that can cause diseases such as acute hepatopancreatic necrotic disease (AHPND), resulting in significant losses to the shrimp farming industry.MethodsIn this study, We analyzed two shrimp populations by transcriptomics and non-targeted metabolomics, which exhibited significant differences in resistance to VP. Through integrated analysis, we identified genes and metabolites linked to the development of shrimp's resistance to VP.Results and discussionThe analysis revealed that the differential metabolism of flavonoid compounds, especially quercetin, significantly influences the expression of shrimp's resistance to VP. Supplementing feed with an appropriate quantity of quercetin has the potential to increase the expression of crucial genes in the NF-κB pathway, including TLR and AP1, along with the expression of the antibacterial peptide crustin, resulting in a decreased mortality rate. Together, these results indicate that an appropriate amount of quercetin can strengthen the immune response of shrimp to VP, thereby reducing the incidence of AHPND.

Abstract The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

Abstract Objective : Acute ischemic stroke (AIS) stands as a leading cause of death and disability globally. This study aimed to investigate the risk factors linked with AIS in patients undergoing maintenance hemodialysis (MHD) and to create and validate nomogram models. Methods: We examined the medical records of 314 patients with stage 5 chronic kidney disease (CKD5) undergoing MHD, who sought neurology outpatient department consultation for suspected AIS symptoms between January 2018 and December 2023. These 314 patients were randomly divided into the training cohort (n=222) and validation cohort (n=92). The Least Absolute Shrinkage Selection Operator (LASSO) regression model was employed for optimal feature selection in the AIS risk model. Subsequently, multivariable logistic regression analysis was used to construct a predictive model incorporating the features selected through LASSO. This predictive model's performance was assessed using the C-index and the area under the receiver operating characteristic curve (AUC). Additionally, calibration and clinical utility were evaluated through calibration plots and decision curve analysis (DCA). The model's internal validation was conducted using the validation cohort. Resaults: Predictors integrated into the prediction nomogram encompassed cardiovascular disease (CVD) (Odds Ratio [OR] 7.95, 95% confidence interval [CI] 2.400-29.979), smoking (OR 5.7, 95% CI 1.661-21.955), dialysis time (OR 5.91, 95% CI 5.866-29.979), low-density lipoprotein (LDL) (OR 2.99, 95% CI 0.751-13.007), and fibrin degradation products (FDP) (OR 5.47, 95% CI 1.563-23.162). The model exhibited robust discrimination, with a C-index of 0.877 and 0.915 in the internal training and validation cohorts, respectively. The AUC for the training set was 0.857, and a similar AUC of 0.905 was achieved in the validation cohort. Decision curve analysis (DCA) demonstrated a positive net benefit within a threshold risk range of 2 to 96%. Conclusion: The proposed nomogram effectively identifies MHD patients at high risk of AIS at an early stage. This model holds the potential to aid clinicians in making preventive recommendations.

Distant hybridization is a traditional and effective technology in fish genetic breeding. In this study, we reported a new type of golden pompano (Named as Chenhai No.1) produced by the distant hybridization of (Trachinotus ovatus ♀ ​× ​T. blochii ♂) ♀ ​× ​T. ovatus ♂. The results regarding DNA content, chromosomal number, and morphological traits showed that “Chenhai No.1” was a diploid hybrid with 48 chromosomes, and presented a hybrid appearance compared with those in its parents. Meanwhile, all detected “Chenhai No.1” including males and females showed the normal gonadal structure and could produce offspring by self-crossing at 3 years old. In addition, the growth rate of “Chenhai No.1” was 35.52% faster than T. ovatus. In conclusion, the fertile “Chenhai No.1” with faster growth rate provided a superior germplasm resource, which will further promote the industrial development of golden pompano.

IntroductionThe rapid development of the Litopenaeus vannamei industry largely depends on the acquisition of high-quality larvae. Shrimp larval development is a unique metamorphic process that results in mortality due to disease vulnerability. Currently, studies on innate immunity in shrimp are mainly focused on the adult stage, but little has been done on innate immunity in larvae.MethodsIn this study, utilizing a high-throughput Illumina sequencing approach, we compare the transcriptome of L. vannamei Zoea larvae and adults infected by Vibrio parahaemolyticus.ResultsA total of 487,887,650 high quality reads were obtained, assembled, and aggregated into 23,802 genes, among which 3315 were identified as differentially expressed genes. Then GO term enrichment analysis, KEGG pathway enrichment analysis and functional gene analysis were performed. We found that pathways that are involved in the innate immune response, such as mTOR signaling pathway, MAPK signaling pathway, and Notch signaling pathway, were more enriched in the Zoea stage compared to the adult stage, suggesting that innate immunity against Vibrio vulnificus may exist during the Zoea larvae stage.Discussionwere more enriched in the Zoea stage compared to the adult stage, suggesting that innate immunity against Vibrio vulnificus may exist during the Zoea larvae stage. These findings will provide useful information for the study of innate immunity in shrimp larvae.

Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ‐binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO‐1 (PDZ) proteins. In this study, we demonstrated that the PDZ protein membrane‐associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) inhibited the Wnt/β‐catenin pathway, and subsequently cervical cancer (CC) cell migration and invasion, via decreasing β‐catenin levels. By reducing MAGI3 protein levels, HPV18 E6 promoted CC cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 was preferentially associated with the downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in CC. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in CC progression.

PurposeUnstable femoral shaft fractures (UFSFs) in children aged 5–11 years remain challenging due to their intrinsic instability. The aim of this study was to evaluate the clinical and radiographic outcomes of UFSF in children aged 5 to 11 years managed by the combined use of ESIN and temporary EF.MethodsChildren with UFSF (long oblique and comminuted) treated by ESIN and temporary EF were retrospectively reviewed. Sex, age at injury, side involved, type of fracture, presence or absence of associated lesions or neurovascular complications, type of treatment, time from trauma to surgery, duration of surgery, radiation exposure and length of postoperative immobilization were collected from the medical charts. Radiological and functional outcomes were evaluated according to Beaty's and Flynn's criteria, respectively.ResultsA total of 28 consecutive patients with closed or open (Gustilo type I or II) UFSF were reviewed (18 boys and 10 girls). The mean age at injury was 8.7 ± 1.6 years (range, 5–11); the average weight was 38.1 ± 7.6 kg (range, 26–55). The mean hospital stay was 3.7 ± 1.4 days (range, 2–7), and the mean time to EF and ESIN removal was 6.5 ± 1.1 weeks (range, 4–8) and 9.4 ± 1.6 months (range, 6–12), respectively. Twenty-seven out of 28 patients had excellent radiographic outcomes according to Beaty's criteria, and 24/28 had excellent functional outcomes according to Flynn's criteria. Overall, 4 complications (14.3%) were recorded. No statistically significant correlation was found between complication rates and sex, age, weight or fracture characteristics (P < 0.05).ConclusionsThe combined use of ESIN and temporary EF provides good clinical and radiological outcomes in children with UFSF aged between 5 and 11 years, with a reduced complication rate.

BackgroundMuch observational research reported that tea consumption decreases the risk of osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) which are the three major bone disorders. However, the observed correlation is inconclusive. To determine the causal relationship between genetically predicted tea intake and OA, RA, and OP, we performed a two-sample Mendelian randomization (MR) study based on large samples.MethodsThe European population’s genome-wide association meta-analysis (GWAS) dataset identified SNPs associated with tea consumption was obtained from Neale Lab’s analysis of UK Biobank data that comprised 349,376 participants of European ancestry. We extracted genetic data for knee OA (17,885 controls and 4,462 cases), hip OA (50,898 controls and 12,625 cases), and RA (43,923 controls and 14,361 cases) from the UK Biobank and OP cases (93083 controls and 1,175 cases) from FinnGen Data Freeze 2. A MR study was conducted to examine the effect of selected single nucleotide polymorphisms (SNPs) and OA, RA, and OP risk. Several sensitivity analyses were performed with weighted median and inverse-variance weighted methods for estimating the causal effects.ResultsIn this MR study, the genetically predicted per one cup increase of tea consumption was not associated with knee OA (OR 1.11,95% CI: 0.79–1.55) using IVW with random effect. Genetic predisposition to tea consumption was not associated with hip OA (OR: 1.20, 95% CI: 0.84–1.71), RA (OR: 1.24 95% CI: 0.81–1.91), and OP (OR: 1.11, 95% CI: 0.89, 1.39). Following the sensitivity analysis, there was no potential pleiotropy.ConclusionAccording to our study, According to our study, there was no statistical power to confirm a causal relationship between tea consumption and the risk of knee OA, hip OA, RA, and OP.

Fast and accurate pile volume estimation is a very important basic problem in mining, waste sorting, and waste disposing industry. Nevertheless, for rapid changing or badly conditioned piles like stockpiles or landfills, conventional approaches involving massive measurements may not be applicable. To solve these problems, in this work, by utilizing unmanned aerial vehicles and unmanned ground vehicles equipped with a camera, we propose a collaborative framework to estimate volumes of free-formed piles accurately in short time. Compensating aerial- and ground views enable the reconstruction of piles with steep sides that is hard to be observed by single unmanned aerial vehicle. With the help of red-green-blue image sequences captured by unmanned aerial vehicles, we are able to distinguish piles from the ground in reconstructed point clouds and automatically eliminate concave on the ground while estimating pile volume. In the experiments, we compared our method to state-of-the-art dense reconstruction photogrammetry approaches. The results show that our approach for pile volume estimation has proved its feasibility for industrial use and its availability to free-formed piles on a different scale, providing high-accuracy estimation results in short time.

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch‐like enoyl-coenzyme A hydratase (ECH)‐associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

The existing literature has revealed the questionable economic benefits of hosting such events, while scholars would still hold an optimistic view of the benefits of place branding and promotion. This paper raises a critical question to this view by examining the effectiveness of hosting pro-tourism events for destination branding. This paper collects massive tourist online reviews and conducts sentiment analysis to examine this issue based on the case of Sanya city in China. The study finds that: (1) there is no solid evidence to show that Sanya’s tourism-related events have a significant positive impact on its destination branding; (2) in the short term, that is fewer than six months, culture-related events were more effective in improving the destination’s image; (3) in the long term, that is, from six months to two years, sports-related events had more positive sentiment impacts, while negative sentiment impacts were largely the result of tourist rip-off incidents. In doing so, this paper argues that hosting tourism events would not be a sustainable way of destination branding, unless the event is meant for other interests. This effort provides an innovative approach for understanding the impacts of tourism events to destination branding in a more critical manner.

The uptake of water by contrails in ice-supersaturated air and the release of water after ice particle advection and sedimentation dehydrates the atmosphere at flight levels and redistributes humidity mainly to lower levels. The dehydration is investigated by coupling a plume-scale contrail model with a global aerosol–climate model. The contrail model simulates all the individual contrails forming from global air traffic for meteorological conditions as defined by the climate model. The computed contrail cirrus properties compare reasonably with theoretical concepts and observations. The mass of water in aged contrails may exceed 106 times the mass of water emitted from aircraft. Many of the ice particles sediment and release water in the troposphere, on average 700 m below the mean flight levels. Simulations with and without coupling are compared. The drying at contrail levels causes thinner and longer-lived contrails with about 15 % reduced contrail radiative forcing (RF). The reduced RF from contrails is on the order of 0.06 W m−2, slightly larger than estimated earlier because of higher soot emissions. For normal traffic, the RF from dehydration is small compared to interannual variability. A case with emissions increased by 100 times is used to overcome statistical uncertainty. The contrails impact the entire hydrological cycle in the atmosphere by reducing the total water column and the cover by high- and low-level clouds. For normal traffic, the dehydration changes contrail RF by positive shortwave and negative longwave contributions on the order of 0.04 W m−2, with a small negative net RF. The total net RF from contrails and dehydration remains within the range of previous estimates.