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Cowries (Family Cypraeidae) are widely distributed in tropical and subtropical seas, with the highest diversity of cowries in the Indo-Pacific region. However, the classification of Cypraeidae, especially at the lower taxonomic levels, is still controversial. In the present study, we determined the complete mitochondrial genomes of 10 cowries. All the newly sequenced mtDNA encode 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and several non-coding regions. The reconstructed mitogenomic phylogeny of Cypraeidae recognized two monophyletic clades, with the first clade comprised of Erroneinae, Cypraeinae and Luriinae and the second clade formed by the single subfamily Erosarinae. The congeneric genetic distance values fall within 0.118–0.144, lower than those above genus level ranging from 0.163 to 0.271, consistent with the current division of genera within Cypraeidae. The divergence time estimated here indicated that the ancestor of Indo-Pacific cowries diversified during the Paleocene, and the closure of the Tethys Seaway might lead to the speciation events of several Indo-Pacific species. This study suggests that the complete mtDNA is a promising tool to improve the phylogenetic resolution of Cypraeidae, and mtDNA could also provide important information for future species delimitation especially within the cowries that possess different morphological phenotypes.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.MethodsWe retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.ResultsOverall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].ConclusionsLaparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.

BackgroundThe specific efficacy of immunotherapy for patients with liver metastases of gastric cancer is unclear. This study set out to explore the treatment response and related prognostic factors for patients with liver metastases of gastric cancer treated with immunotherapy.Patients and methodsThis retrospective cohort study included 135 patients with unresectable advanced gastric cancer. According to the presence of liver metastases and/or first-line treatment with immunotherapy, patients were divided into the following three groups: I-LM(-) group(patients without liver metastases treated with immunotherapy, n=66), I-LM(+) group(patients with liver metastases treated with immunotherapy, n=36), C-LM(+) group(patients with liver metastases treated with chemotherapy and/or target therapy, n=33). Cox regression analyses were used to identify factors associated with survival in all patients and the three groups, respectively.ResultsFor the patients with liver metastases treated with immunotherapy, multivariate analysis showed that only the presence of peritoneal metastases was significantly associated with shorter PFS [hazard ratios (HR), 3.23; 95% CI, 1.12-9.32; P=0.030] and the patients with peritoneal metastases had shorter median PFS than patients without peritoneal metastases(3.1 vs 18.4 months; P=0.004), while the objective response rate was 100% in patients with HER2-positive (2 complete radiographic responses and 2 partial responses; 3 of 4 patients were still ongoing benefits [median follow-up time, 15.3 months ; interquartile range(IQR), 6.3-17.9 months]).ConclusionsThe findings suggest that patients with various types of gastric cancer liver metastases respond differently to immune checkpoint inhibitors, HER2-positive patients may derive clinical benefits from immune checkpoint inhibitors, while the presence of peritoneal metastases is associated with resistance.

The marine gastropod Strombidae is widely distributed in tropical and subtropical regions all over the world and possesses high morphological diversity. In order to better understand how morphological characteristics evolved within Strombidae, a robust phylogenetic framework is needed. In the present study, the complete mitochondrial genomes of Lentigo lentiginosus, Euprotomus aratrum, and Canarium labiatum were sequenced. The three newly sequenced mt genomes contained 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and several non-coding regions, indicating a similar pattern with respect to genome size, gene order, and nucleotide composition compared with those of other strombids reported before. Two different datasets derived from mitochondrial genes were constructed to resolve the internal phylogenetic relationships of Stromboidea and Strombidae. Within Stromboidea, the sister group formed by Clade I [Rostellariidae + (Seraphsidae + Strombidae)] and Clade II [Xenophoridae + (Struthiolariidae + Aporrhaidae)] were fully recovered and supported by morphological synapomorphies as previously suggested. The phylogenetic positions of L. lentiginosus, E. aratrum, and C. labiatum were confirmed within Strombidae, and several morphological similarities were observed corresponding to the present phylogeny. A correlation between strombids speciation events and paleoclimate change was presumed. Our results indicate that complete mt genomes would be a promising tool to reconstruct a robust phylogeny of Strombidae with an increased taxon sampling in the future.

BackgroundSeveral observational studies have indicated an association between interstitial cystitis and the composition of the gut microbiota; however, the causality and underlying mechanisms remain unclear. Understanding the link between gut microbiota and interstitial cystitis could inform strategies for prevention and treatment.MethodsA two-sample Mendelian randomization analysis was conducted using published genome-wide association study summary statistics. We employed inverse variance weighted, weighted mode, MR-Egger, weighted median, simple mode, and cML-MA methods to investigate the causal relationship between gut microbiota and interstitial cystitis. Sensitivity analysis was performed to validate the results. Relevant gut microbiota was examined through reverse MR. Single nucleotide polymorphisms were annotated using FUMA to identify genes associated with these genetic variants, thereby revealing potential host gene-microbiota associations in interstitial cystitis patients.ResultsEight bacterial taxa were identified in our analysis as associated with interstitial cystitis. Among these, Butyricimonas, Coprococcus, Lactobacillales, Lentisphaerae, and Bilophila wadsworthia were positively correlated with interstitial cystitis risk, while taxa such as Desulfovibrio piger, Oscillibacter unclassified and Ruminococcus lactaris exhibited protective effects against interstitial cystitis. The robustness of these associations was confirmed through sensitivity analyses. Reverse MR analysis did not reveal evidence of reverse causality. Single nucleotide polymorphisms were annotated using FUMA and subjected to biological analysis. Seven hub genes (SPTBN1, PSME4, CHAC2, ERLEC1, ASB3, STAT5A, and STAT3) were identified as differentially expressed between interstitial cystitis patients and healthy individuals, representing potential therapeutic targets.ConclusionOur two-sample Mendelian randomization study established a causal relationship between gut microbiota and interstitial cystitis. Furthermore, our identification of a host gene-microbiota association offers a new avenue for investigating the potential pathogenesis of interstitial cystitis and suggests avenues for the development of personalized treatment strategies.

BackgroundTo establish antibiotic preregimes and administration routes for studies on urinary microbiota.Methods and materialsAntibiotics for enteritis (Abx-enteritis) and UTIs (Abx-UTI) were administered via gavage and/or urinary catheterisation (UC) for 1 and/or 2 weeks. The effects of these Abx on the urinary microbiota of rats were examined via 16S rRNA sequencing and urine culture, including anaerobic and aerobic culture. Additionally, the safety of the Abx was examined.ResultsAbx-enteritis/Abx-UTI (0.5 g/L and 1 g/L) administered via gavage did not alter the microbial community and bacterial diversity in the urine of rats (FDR > 0.05); however, Abx-UTI (1 g/L) administered via UC for 1 and 2 weeks altered the urinary microbial community (FDR < 0.05). Rats administered Abx-UTI (1 g/L) via UC for 1 week demonstrated a distinct urinary microbiota in culture. Abx-enteritis/Abx-UTI administered via gavage disrupted the microbial community and reduced bacterial diversity in the faeces of rats (FDR < 0.05), and Abx-UTI administered via UC for 2 weeks (FDR < 0.05) altered the fecal microbiota. Abx-UTI (1 g/L) administered via UC did not alter safety considerations. In addition, we noticed that UC did not induce infections and injuries to the bladder and kidney tissues.ConclusionsAdministration of Abx-UTI via UC for 1 week can be considered a pre-treatment option while investigating the urinary microbiota.

Ferredoxin 1 (FDX1) functions by transferring electrons from NADPH to mitochondrial cytochrome P450 via the ferredoxin reductase and is the key regulator in copper-dependent cell death. Although mounting evidence supports a vital role for FDX1 in tumorigenesis of some cancers, no pan-cancer analysis of FDX1 has been reported. Therefore, we aimed to explore the prognostic value of FDX1 in pan-cancer and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, Human Protein Atlas, and Gene Set Cancer Analysis, we used a range of bioinformatics approaches to explore the potential carcinogenic role of FDX1, including analyzing the relationship between FDX1 expression and prognosis, DNA methylation, RNA methylation-related genes, mismatch repair (MMR) gene, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), immune-related genes, and drug sensitivity in different tumors. The results show that FDX1 was lowly expressed in most cancers but higher in glioblastoma multiforme, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Moreover, FDX1 expression was positively or negatively associated with prognosis in different cancers. FDX1 expression was significantly associated with DNA methylation in 6 cancers, while there was a correlation between FDX1 expression and RNA methylation-related genes and MMR gene in most cancers. Furthermore, FDX1 expression was significantly associated with MSI in 8 cancers and TMB in 10 cancers. In addition, FDX1 expression was also significantly correlated with immune cell infiltration, immune-related genes, TME, and drug resistance in various cancers. An experiment in vitro showed FDX1 is downregulated by elesclomol, resulting in inhibiting cell viability of bladder cancer, clear cell renal cell carcinoma, and prostate cancer cells. Our study reveals that FDX1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

ObjectivesMounting evidence suggests that bacterial dysbiosis and immunity disorder are associated with patients with chronic kidney disease (CKD), but the mycobiome is beginning to gain recognition as a fundamental part of our microbiome. We aim to characterize the profile of the mycobiome in the gut of CKD patients and its correlation to serum immunological profiles.Methods and materialsNinety-two CKD patients and sex–age–body mass index (BMI)–matched healthy controls (HCs) were recruited. Fresh samples were collected using sterile containers. ITS transcribed spacer ribosomal RNA gene sequencing was performed on the samples. An immunoturbidimetric test was used to assess the serum levels of immunological features.ResultsThe CKD cohort displayed a different microbial community from that in the HC cohort according to principal coordinate analysis (PCoA). (P=0.001). The comparison of the two cohorts showed that the CKD cohort had significantly higher gut microbial richness and diversity (P

Alterations in the microbiome of the gut and oral cavity are involved in the etiopathogenesis of systemic lupus erythematosus (SLE). We aimed to assess whether both microbiome compositions in feces and saliva were specific in patients with SLE. A total of 35 patients with SLE, as well as sex- and age-matched asymptomatic subjects as healthy control (HC) group were recruited. Fecal swabs and saliva samples were collected from the participants. 16S ribosomal RNA gene sequencing was performed on the samples. Compared with the HC group, reduced bacterial richness and diversity were detected in the feces of patients with SLE, and increased bacterial diversity in their saliva. Both feces and saliva samples explained the cohort variation. The feces were characterized by enrichment of Lactobacillus, and depletion of an unclassified bacterium in the Ruminococcaceae family and Bifidobacterium. Lack of Bifidobacterium was observed in patients with arthritis. Akkermansia and Ruminococcus negatively correlated with the serum levels of C3. In saliva, Veillonella, Streptococcus, and Prevotella were dominant, and Bacteroides was negatively associated with disease activity. These findings can assist us to comprehensively understand the bacterial profiles of different body niches in SLE patients.

ObjectivesGut dysbiosis is associated with chronic kidney disease (CKD), and serum free immunoglobulin light chains (FLCs) are biomarkers for CKD. This study aims to assess the CKD gut microbiome and to determine its impact on serum FLC levels.MethodsTo control for confounders, 100 patients and sex- and age-matched healthy controls (HCs) were recruited. The gut microbiome was assessed by sequencing 16S rRNA gene V3-V4 hypervariable regions. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was applied to infer functional metabolic pathways. When observing group differences in the microbiome and predicted metabolic pathways, demographic confounders were adjusted using binary logistic regression; when examining impacts of the gut microbiome and metabolic pathways on serum FLCs, factors influencing FLC levels were adjusted using multiple regression.ResultsPrincipal coordinate analysis revealed a significantly different bacterial community between the CKD and HC groups (P < 0.05). After adjusting for confounders, lower Chao 1, observed species and Shannon indices based on binary logistic regression predicted CKD prevalence. Actinobacteria, Alistipes, Bifidobacterium and Bifidobacterium longum enrichment, upregulation of metabolic pathways of bacterial toxin, chloroalkane and chloroalkene degradation, and Staphylococcus aureus infection also predicted CKD prevalence (P < 0.05). Furthermore, depletion of Actinobacteria and Bifidobacterium and reduced chloroalkane and chloroalkene degradation predicted high levels of FLC λ (P < 0.05).ConclusionsGut dysbiosis in CKD patients was confirmed by controlling for confounders in the present study. Additionally, the association between gut dysbiosis and FLC λ levels demonstrates the existence of crosstalk between the microbiome and immune response in CKD.

Owing to the avascular structure of the ovarian follicle, proliferation of granulosa cells (GCs) and development of follicles occur under hypoxia, which is obviously different from the cell survival requirements of most mammalian cells. We hypothesized that autophagy may exert an inhibitory effect on GC apoptosis. To decipher the underlying mechanism, we constructed a rat follicular development model using pregnant mare serum gonadotropin and a cell culture experiment in hypoxic conditions (3% O2). The present results showed that the autophagy level was obviously increased and was accompanied by the concomitant elevation of hypoxia inducible factor (HIF)-1α and BNIP3 (Bcl-2/adenovirus E1B 19kDa-interacting protein 3) in GCs during follicular development. The levels of Bax (Bcl2-associated X) and Bcl-2 (B-cell lymphoma-2) were increased, while the activation of caspase-3 exhibited no obvious changes during follicular development. However, inhibition of HIF-1α attenuated the increase in Bcl-2 and promoted the increase in Bax and cleaved caspase-3. Furthermore, we observed the downregulation of BNIP3 and the decrease in autophagy after treatment with a specific HIF-1α activity inhibitor (echinomycin), indicating that HIF-1α/BNIP3 was involved in autophagy regulation in GCs in vivo. In an in vitro study, we also found that hypoxia did not obviously promote GC apoptosis, while it significantly enhanced the activation of HIF-1α/BNIP3 and the induction of autophagy. Expectedly, this effect could be reversed by 3-methyladenine (3-MA) treatment. Taken together, these findings demonstrated that hypoxia drives the activation of HIF-1α/BNIP3 signaling, which induces an increase in autophagy, protecting GC from apoptosis during follicular development.

In mammals, developing ovarian follicles transform from primordial follicles to primary follicles, secondary follicles, and mature follicles, accompanied by changes in follicular secretory functions. FoxO3a is a member of the forkhead transcription factor family (FoxO), which plays an important role in the cell cycle, DNA damage repair, apoptosis, oxidative stress, and energy metabolism. Recent studies have shown that FOXO3a is involved in the physiological regulation of follicular development and pathological progression of related ovarian diseases, which will provide useful concepts and strategies for retarding ovarian aging, prolonging the ovarian life span, and treating ovarian diseases. Therefore, the regulation of FOXO3a expression, as well as the physiological contribution during ovarian follicular development are detailed in this paper, presenting an important reference for the further study of ovarian biology.

Gut metabolites are products of the crosstalk between microbes and their host and play an important role in the occurrence, development, diagnosis, and treatment of autoimmune diseases. This work profiled the fecal metabolome of patients with systemic lupus erythematosus (SLE) using gas chromatography–mass spectrometry (GC-MS) and analyzed the potential roles of metabolites in the diagnosis and development of SLE. Fecal sample from 29 SLE patients without any other diseases and 30 healthy controls (HCs) were analyzed by metabolomics profiling. All participants took no antibiotics in the month before sampling and clinical data collecting. The metabolome profiles of patients with SLE and HCs were significantly different. Thirty fecal metabolites, such as deoxycholic acid, erucamide, L-tryptophan and putrescine, were significantly enriched, while nine metabolites, such as glyceric acid, γ-tocopherol, (Z)-13-octadecenoic acid and 2,4-di-tert-butylphenol, were depleted in SLE patients vs. HCs. The areas under the curve (AUCs) of L-valine, pyrimidine, erucamide, and L-leucine during ROC analysis were 0.886, 0.833, 0.829, and 0.803, indicating their good diagnostic potential. Moreover, the combination of L-valine, erucamide and 2,4-di-tert-butylphenol gave an AUC of 0.959. SLE-altered metabolites were significantly located in 28 pathways, such as ABC transporters (p = 3.40E-13) and aminoacyl-tRNA biosynthesis (p = 2.11E-12). Furthermore, SLE-altered fecal metabolites were closely correlated with SLE indicators, e.g., L-tryptophan was positively correlated with the SLEDAI-2K (p = 0.007). Our results suggest that the SLE fecal metabolome is closely associated with the occurrence and development of SLE and is of great diagnostic value.

Similar to the gut, the bladder contains urinary microbiota, and its bacterial composition and structure are determined by the individual’s health status. Cesarean section is a traumatic event for women and it is correlated with postpartum complications. To better understand the urinary microbiota alterations caused by cesarean section, 16S rDNA sequencing was used to assess urine specimens collected by transurethral catheterization from 30 healthy women undergoing cesarean section pre-delivery (PreD) and post-delivery (PostD). A significant increase in bacterial diversity and more detectable bacteria at the phylum, family, and genus levels was observed in the PostD group compared to the PreD group, indicating that cesarean delivery (a process that includes surgery and delivery) altered the bacterial community. Specifically, the phylum Firmicutes and its affiliated family Lactobacillaceae and genus Lactobacillus dramatically decreased in the PostD group, suggesting that beneficial bacteria decreased after cesarean section, and clinicians should be aware that this might increase the risk of complications. Concurrently, the phylum Proteobacteria and its affiliated bacteria Pseudomonadaceae and Pseudomonas increased in the PostD group compared to the PreD group. This indicates that pathogen growth increases after cesarean section, making it important for clinicians to combat these changes to protect women from infectious diseases. Interestingly, several metabolic pathways, such as metabolism of energy, cofactors and vitamins were strengthened in the PostD group, whereas membrane transport was lessened in this group. This suggests that women’s metabolic disorders might be cured by balancing urinary microbiota. In conclusion, the altered urinary microbiota between the PreD and PostD periods appears to provide insight into how to prevent postpartum metabolic disorders.

Evidence has shown that dysbiosis of the urinary microbiota existed in female type 2 diabetes mellitus (T2DM) patients. Perturbations of intestinal microbiota are linked to proinflammatory chemokine interleukin-8 (IL-8); however, the correlations between urinary microbiota and IL-8 are not well studied. Here, we investigated the associations between the altered urinary microbiota and urinary IL-8 in female T2DM patients. A modified four-tube midstream urine technique was used to collect urine specimens from 70 female T2DM patients and 70 matched healthy controls (HCs). Bacterial genomic DNA from urine specimens was isolated using magnetic beads and the urinary microbiota was assessed using Illumina MiSeq platform targeting on the 16S rRNA gene V3–V4 region. Urinary IL-8 was determined by enzyme linked immunosorbent assay. Subsequently, the T2DM patients were separated into urine IL-8 detectable (WIL8) and undetectable (NIL8) groups, and the composition of urinary microbiota between the two groups was compared. Meanwhile, the levels of IL-8 between the “≥HCs” group (those specific bacterial genera were more than or equal to the HCs) and the “