Sex differences in colorectal cancer: with a focus on sex hormone-gut microbiome axis.

Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of 'microgenderome' and 'sex hormone-gut microbiome axis.' Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone-gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment.

A new cavefish of Sinocyclocheilus (Teleostei: Cypriniformes: Cyprinidae) from the Nanpanjiang River in Guizhou, China.

A new species, Sinocyclocheilus xingyiensis, is described based on specimens collected from a karst cave in Guizhou Province, China. The authors used an integrated taxonomic approach, including morphological and molecular data, to identify the new species as a member of the Sinocyclocheilu angularis group, and it can be distinguished from all other members of this group by a combination of the following features: two pairs of long barbels and long pectoral fins, 42-46 lateral-line scales, 7 (13-14) on outer (inner) side of the first gill arch and 35 (14-15 + 4 + 16 - 17) vertebrae. Phylogenetic analyses based on the cytochrome b (cyt b) gene fragment suggest that S. xingyiensis is a sister lineage to Sinocyclocheilus flexuosdorsalis. The genetic distance (Kimura 2-parameter) between the S. xingyiensis and S. angularis groups of Sinocyclocheilus species based on cyt b gene fragment ranged from 1.2% to 15.4%.

The New Mitochondrial Genome of Hemiculterella wui (Cypriniformes, Xenocyprididae): Sequence, Structure, and Phylogenetic Analyses.

Hemiculterella wui is an endemic small freshwater fish, distributed in the Pearl River system and Qiantang River, China. In this study, we identified and annotated the complete mitochondrial genome sequence of H. wui. The mitochondrial genome was 16,619 bp in length and contained 13 protein coding genes (PCGs), two rRNA genes, 22 tRNA genes, and one control region. The nucleotide composition of the mitochondrial genome was 29.9% A, 25.3% T, 27.4% C, and 17.5% G, respectively. Most PCGs used the ATG start codon, except COI and ATPase 8 started with the GTG start codon. Five PCGs used the TAA termination codon and ATPase 8 ended with the TAG stop codon, and the remaining seven genes used two incomplete stop codons (T and TA). Most of the tRNA genes showed classical cloverleaf secondary structures, except that tRNASer(AGY) lacked the dihydrouracil loop. The average Ka/Ks value of the ATPase 8 gene was the highest, while the average Ka/Ks value of the COI gene was the lowest. Phylogenetic analyses showed that H. wui has a very close relationship with Pseudohemiculter dispar and H. sauvagei. This study will provide a valuable basis for further studies of taxonomy and phylogenetic analyses in H. wui and Xenocyprididae.

PacBio Full-Length Transcriptome of a Tetraploid Sinocyclocheilus multipunctatus Provides Insights into the Evolution of Cavefish.

Sinocyclocheilus multipunctatus is a second-class nationally protected wild animal in China. As one of the cavefish, S. multipunctatus has strong adaptability to harsh subterranean environments. In this study, we used PacBio SMRT sequencing technology to generate a first representative full-length transcriptome for S. multipunctatus. Sequence clustering analysis obtained 232,126 full-length transcripts. Among all transcripts, 40,487 were annotated in public databases, while 70,300 microsatellites, 2384 transcription factors, and 16,321 long non-coding RNAs were identified. The phylogenetic tree showed that S. multipunctatus shows a closer relationship to Carassius auratus and Cyprinus carpio, phylogenetically diverging from the common ancestor ~14.74 million years ago (Mya). We also found that between 15.6 and 17.5 Mya, S. multipunctatus also experienced an additional whole-genome duplication (WGD) event, which may have promoted the species evolution of S. multipunctatus. Meanwhile, the overall rates of evolutionary of polyploid S. multipunctatus were significantly higher than those of the other cyprinids, and 220 positively selected genes (PSGs) were identified in two sub-genomes of S. multipunctatus. These PSGs are likely to fulfill critical roles in the process of adapting to diverse cave environments. This study has the potential to facilitate future investigations into the genomic characteristics of S. multipunctatus and provide valuable insights into revealing the evolutionary history of polyploid S. multipunctatus.

The Mitochondrial Genome of Linichthys laticeps (Cypriniformes: Cyprinidae): Characterization and Phylogeny.

Mitochondrial genomes (mitogenomes) have been widely used in phylogenetic analysis and evolutionary biology. The Labeoninae is the largest subfamily of Cypriniformes and has great economic importance and ecological value. In this study, we sequenced, annotated, and characterized the complete mitogenome of Linichthys laticeps and then constructed the phylogenetic tree with previously published Labeoninae mitogenomes. The mitogenome of L. laticeps was 16,593 bp in length, with an A + T content of 57.1%. The mitogenome contained a standard set of 37 genes and a control region with the same order and orientation of genes as most fish mitogenomes. Each protein-coding gene (PCG) was initiated by an initial ATG codon, excluding COI, that began with a GTG codon. Furthermore, most of the PCGs were terminated by a conventional stop codon (TAA/TAG), while an incomplete termination codon (TA/T) was detected in 7 of the 13 PCGs. Most tRNA genes in L. laticeps were predicted to fold into the typical cloverleaf secondary structures. The Ka/Ks (ω) values for all PCGs were below one. The phylogenetic relationships of 96 Labeoninae mitogenomes indicated that Labeoninae was not a monophyletic group and L. laticeps was closely related to the genera Discogobio and Discocheilus. Overall, our study provided the first complete annotated mitogenome of L. laticeps, which filled a knowledge gap in Labeoninae and extended the understanding of the taxonomy and mitogenomic phylogeny of the subfamily Labeoninae.

Comprehensive transcripts analysis based on single-molecule real-time sequencing and Illumina sequencing provides insights into the mining of Toll-like receptor family in Schizothorax lissolabiatus.

Schizothorax lissolabiatus is an economically important cold-water fish species in southwestern China. Because of water pollution and habitat destruction, the number of wild populations has dramatically decreased. In this study, we used PacBio single-molecule real-time (SMRT) sequencing and Illumina sequencing to generate the first full-length transcriptome and transcriptome, respectively. A total of 19 310 polished consensus reads (PC) were obtained, with an average length of 1379 bp and an N50 length of 1485 bp. Meanwhile, 12 253 transcripts were successfully annotated as known homologous genes. The pathway annotation indicated that the enrichment and expression of most genes were mainly related to membrane, signal transduction and binding, and immune response. Furthermore, we identified 16 Toll-like receptors (TLRs) by mining the data from the transcripts. Phylogeny analysis showed that S. lissolabiatus TLR genes (slTLRs) supported the classification of TLRs into six families as in other vertebrates. Selection pressure analyses showed that 16 slTLRs revealed purification selection at the overall evolutionary selection. Further, positive selection signals were still detected in eight slTLRs, and most of the positive selection sites were located in the leucine-rich repeat region (LRR domain) associated with the recognition of pathogenic microorganisms, indicating that the function of these slTLR genes may be affected. Tissue specific expression analysis showed all slTLRs are present in kidney, spleen and liver but the relative expression varied among tissues. In conclusion, this study not only provided a valuable resource of transcripts for further research on S. lissolabiatus, but also contributed to improve the current understanding of the evolutionary history of immune-related genes and the TLR gene family in S. lissolabiatus.

Enhancing acid-base-water ternary aerosol nucleation with organic acid: a case of tartaric acid.

The new particle formation (NPF) process has been observed globally in clean and polluted environments, where the fundamental mechanisms leading to multicomponent aerosol formation remain elusive. Dicarboxylic acids play an important role in atmospheric NPF. In this study, theoretical calculations are performed to assess the effect of tartaric acid (TA) on the formation of clusters consisting of sulfuric acid (SA), ammonia (AM) or amines (methylamine or dimethylamine, MA/DMA) in the presence of water. Both carboxyl groups and hydroxyl groups in the carbon chain of TA could be involved in hydrogen bonds. The presence of TA triggers proton transfer from SA to the base molecule to form new covalent bonds or strengthens the preexisting covalent bonds, hence, all the hydrated (SA)(TA)(base) cluster formations by adding one TA molecule to the (SA)(base) hydrates are energetically favorable. The dipole-dipole interaction is not only related to the Gibbs energy change for acid affinity reactions to (SA)(W)n and (SA)(base)(W)n (n = 0-4) clusters but also positively related to the reaction rate constant. These results combined with preliminary kinetic results indicate that TA is very likely to participate in clustering and promote subsequent growth involving hydrated SA and (SA)(base) clusters. In addition, our results further indicate that the NPF process can be promoted by multicomponent nucleation involving organic acids, SA, and base species, which will help in understanding NPF in polluted areas and improving global and regional models.

The Complete Mitochondrial Genome of the Freshwater Fish Onychostoma ovale (Cypriniformes, Cyprinidae): Genome Characterization and Phylogenetic Analysis.

In this study, we sequenced and characterized the complete mitochondrial genome (mitogenome) of Onychostoma ovale. The mitogenome of O. ovale was 16,602 bp in length with 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region. The nucleotide composition of the O. ovale mitogenome was 31.47% A, 24.07% T, 15.92% G, and 28.54% C, with a higher A + T content (55.54%) than G + C content (44.46%). All PCGs began with the standard ATG codon, except for the cytochrome c oxidase subunit 1 (COX1) gene and the NADH dehydrogenase 3 (ND3) gene with GTG, while six PCGs ended with incomplete termination codons (TA or T). The Ka/Ks ratios of 13 PCGs were all less than one, indicating that they were under purifying selection. All tRNA genes were folded into the typical cloverleaf secondary structures with the exception of tRNASer(AGY), whose dihydrouridine (DHU) arm was absent. The phylogenetic trees showed that Onychostoma and Acrossocheilus were classified into three clades. There was a mosaic relationship between Onychostoma and Acrossocheilus. Moreover, the phylogenetic tree analysis showed that O. rarum was the closest species to O. ovale. This study can provide a useful resource for further phylogeny and population genetic analyses of Onychostoma and Acrossocheilus.

Comparison of the Efficacy of Endoscopic Radial Incision and Cutting Procedure and Endoscopic Balloon Dilation for Benign Anastomotic Stricture After Low Anterior Resection Combined With Preventive Loop Ileostomy in Rectal Cancer.

BACKGROUND: Endoscopic radial incision and cutting procedure is a notable technique in the treatment of benign anastomotic strictures after low anterior resection in rectal cancer. However, the efficacy and safety of the endoscopic radial incision and cutting procedure and traditional endoscopic balloon dilation remain unknown. OBJECTIVE: To compare the efficacy and safety of the endoscopic radial incision and cutting procedure and endoscopic balloon dilation in patients with anastomotic stricture after low anterior resection. DESIGN: Rectal cancer patients with anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy between January 2014 and June 2021 were retrospectively collected. These patients underwent the endoscopic radial incision and cutting procedure or endoscopic balloon dilation as an initial treatment. The clinicopathological baseline data of the patients, endoscopic surgery success rate, complications, and restricture rate were analyzed. SETTINGS: This study was conducted at Nanfang Hospital in China. PATIENTS: A total of 30 patients were eligible after reviewing the medical records. Twenty patients underwent endoscopic balloon dilation, and 10 patients underwent endoscopic radial incision and cutting procedure. MAIN OUTCOME MEASURES: The adverse event rate and stricture recurrence rate. RESULTS: There were no significant differences in patient demographics or clinical features. No adverse events occurred in either of the 2 groups. The mean operation time was 18.9 ± 3.6 minutes in the endoscopic balloon dilation group and 10.2 ± 3.3 minutes in the endoscopic radial incision and cutting procedure group ( p < 0.001). The stricture recurrence rates between the endoscopic balloon dilation group and the endoscopic radial incision and cutting procedure group were significantly different (44.4% vs 0%; p = 0.025). LIMITATIONS: This was a retrospective study. CONCLUSIONS: The endoscopic radial incision and cutting procedure is safe and more efficacious than endoscopic balloon dilation for anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy in rectal cancer.

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy.

BACKGROUND: Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, [Formula: see text] 100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity. RESULTS: Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5-13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1ß (IL-1 [Formula: see text]) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer. CONCLUSIONS: Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

INTRODUCTION: In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients. PATIENTS AND METHODS: In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m2 subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m2 orally; and prednisone 60 mg/m2 orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression. RESULTS: After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%). CONCLUSION: D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www. CLINICALTRIALS: gov as #NCT03217812.

Association of plasma lipid metabolism profiles with overall survival for patients with gastric cancer undergoing gastrectomy based on 1H-NMR spectroscopy.

BACKGROUND: Lipid metabolism dysregulation is a prominent metabolic alteration in various cancers. The study aimed to explore the association of plasma lipid metabolism profiles with overall survival (OS) for gastric cancer (GC) patients who received gastrectomy. METHODS: GC patients who were treated with gastrectomy and measured with plasma lipid metabolism profiles using proton nuclear magnetic resonance (1H-NMR) spectroscopy in Nanfang Hospital between January 1, 2017, and October 31, 2018, were recruited. The Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to analyze variables selected by univariate analysis for OS. An index of plasma lipid metabolism profiles, named plasma lipid metabolism index (PLMI), was constructed by variables' coefficients in LASSO regression to explore its association with OS and its role in the prediction model. RESULTS: A total of 158 GC patients were included in this study. Four of the 110 lipid profiles, including LDL-5 Apo-B, LDL-4 Cholesterol, HDL-4 Apo-A2, and HDL-4 Free Cholesterol, were selected to construct the PLMI. The optimal cut-off value of PLMI for OS was used to classify the population into two subgroups, the high PLMI group (≥ - 0.163) and the low PLMI group (< - 0.163). The high PLMI group had a shorter OS (p = 0.0034) and was the independent risk factor for OS (Hazard Ratio = 2.13, 95% Confidence Interval (CI): 1.07-4.22, p = 0.031) after adjusting for perineural invasion and tumor stage. In subsets of the I-III stage and treating postoperative chemotherapy, high PLMI also had an unfavorable correlation with OS (p = 0.016 and p = 0.0086, respectively). The nomogram prediction models of both the training cohort and validation cohort showed good calibration and discrimination with the concordance indexes of 0.806 (95% CI, 0.732-0.880) in the training cohort and 0.794 (95% CI, 0.725-0.862) in the validation cohort. CONCLUSIONS: This study found that the index derived from the LDL-5 Apo-B, LDL-4 Cholesterol, HDL-4 Apo-A2, and HDL-4 Free Cholesterol, was significantly associated with overall survival, suggesting that regulating lipid metabolisms might improve the prognosis for GC patients.

Association of peripheral basophils with tumor M2 macrophage infiltration and outcomes of the anti-PD-1 inhibitor plus chemotherapy combination in advanced gastric cancer.

BACKGROUND: Although the anti-programmed death-1 (PD-1) inhibitor plus chemotherapy combination has been approved as the standard first-line treatment for advanced gastric cancer, a proportion of patients do not significantly benefit from this therapy. Who would respond poorly to this treatment and the underlying mechanisms of treatment failure are far from clear. METHODS: We retrospectively analyzed the associations between the peripheral basophils at baseline and clinical outcomes in 63 advanced gastric cancer patients treated with anti-PD-1 plus chemotherapy and 54 patients treated with chemotherapy alone. Immunohistochemistry and immunofluorescence staining in gastric cancer samples were utilized to investigate the basophil-related immunophenotype. RESULTS: The optimal cutoff of basophil count to distinguish responders to anti-PD-1 plus chemotherapy from non-responders was 20.0/µL. Compared with the low basophil group (≤ 20.0/µL, n = 40), the high basophil group (> 20.0/µL, n = 23) had a significantly lower objective response rate (ORR 17.4% vs. 67.5%, p = 0.0001), worse progression-free survival (median PFS 4.0 vs. 15.0 months, p = 0.0003), and worse overall survival (median OS not reached, p = 0.027). Multivariate analyses identified a basophil count of > 20.0/µL as an independent risk factor for a worse ORR (OR 0.040, 95% CI 0.007-0.241, p = 0.0004), worse PFS (HR 3.720, 95% CI 1.823-7.594, p = 0.0003) and worse OS (HR 3.427, 95% CI 1.698-6.917, p = 0.001). In contrast, there was no significant association between peripheral basophil counts and tumor response or survival in the chemotherapy-alone group (p > 0.05). In primary gastric cancer samples, we observed a correlation between higher peripheral basophil counts and the accumulation of tumor-infiltrating basophils (r = 0.6833, p = 0.005). Tumor-infiltrating basophils were found to be spatially proximate to M2 macrophages within TME and positively correlated with tumor M2 macrophage infiltration (r = 0.7234, p = 0.0023). The peripheral basophil counts also had a significant positive correlation with tumor-infiltrating M2 macrophage counts (r = 0.6584, p = 0.003). Further validation in tumor samples treated with the neoadjuvant anti-PD-1 inhibitor plus chemotherapy combination suggests that the peripheral basophils, tumor infiltration of basophils, and M2 macrophages were significantly more abundant in non-responders than in responders (p = 0.0333, p = 0.0007, and p = 0.0066, respectively). CONCLUSIONS: The peripheral basophil count was observed to be a potential biomarker of anti-PD-1 efficacy for advanced gastric cancer. Moreover, basophils may induce an immune-evasive tumor microenvironment by increasing M2 macrophage infiltration, which could be a potential immunotherapeutic target for advanced gastric cancer.

In Utero Ultrafine Particulate Exposure Yields Sex- and Dose-Specific Responses to Neonatal Respiratory Syncytial Virus Infection.

Exposure to particulate matter (PM) is associated with lower respiratory tract infections. The role of ultrafine particles (UFPs, ≤0.1 µm) in respiratory disease is not fully elucidated, especially in models of immunologically immature populations. To characterize the effects of maternal UFP exposure on neonatal infection, we exposed time-mated C57Bl/6n mice to filtered air or UFPs at a low dose (LD, ∼55 µg/m3) and high dose (HD, ∼275 µg/m3) throughout gestation. At 5 days of age, offspring were infected with a respiratory syncytial virus (RSV) strain known to mimic infant infection or sham control. Offspring body weights were significantly reduced in response to infection in the LD RSV group, particularly females. Pulmonary gene expression analysis demonstrated significantly increased levels of oxidative stress- and inflammation-related genes in HD-exposed male offspring in sham and RSV-infected groups. In males, the highest grade of inflammation was observed in the HD RSV group, whereas in females, the LD RSV group showed the most marked inflammation. Overall, findings highlight neonatal responses are dependent on offspring sex and maternal UFP dose. Importantly, infant RSV pathology may be enhanced following even low dose UFP exposure signifying the importance of preventing maternal exposure.

Heterogeneous iodine-organic chemistry fast-tracks marine new particle formation.

The gas-phase formation of new particles less than 1 nm in size and their subsequent growth significantly alters the availability of cloud condensation nuclei (CCN, >30-50 nm), leading to impacts on cloud reflectance and the global radiative budget. However, this growth cannot be accounted for by condensation of typical species driving the initial nucleation. Here, we present evidence that nucleated iodine oxide clusters provide unique sites for the accelerated growth of organic vapors to overcome the coagulation sink. Heterogeneous reactions form low-volatility organic acids and alkylaminium salts in the particle phase, while further oligomerization of small α-dicarbonyls (e.g., glyoxal) drives the particle growth. This identified heterogeneous mechanism explains the occurrence of particle production events at organic vapor concentrations almost an order of magnitude lower than those required for growth via condensation alone. A notable fraction of iodine associated with these growing particles is recycled back into the gas phase, suggesting an effective transport mechanism for iodine to remote regions, acting as a "catalyst" for nucleation and subsequent new particle production in marine air.