Can proximal gastrectomy with double-tract reconstruction replace total gastrectomy? a meta-analysis of randomized controlled trials and propensity score-matched studies.

BACKGROUND: According to the 5th edition of the Japanese Guidelines for the Treatment of Gastric Cancer, proximal gastrectomy is recommended for patients with early upper gastric cancer who can retain the distal half of the residual stomach after R0 resection. However, a large number of recent clinical studies suggest that surgical indications for proximal gastrectomy in the guidelines may be too narrow. Therefore, this meta-analysis included patients with early and advanced gastric cancer and compared short- and long-term postoperative outcomes between the two groups. At the same time, we only had high-quality clinical studies such as propensity score-matched studies and randomized controlled trials, which made our research more authentic and credible. METHODS: Data were retrieved from PubMed, EMBASE, Medline, and Cochrane Library up to June 2023, and included treatment outcomes after proximal gastrectomy with double-tract reconstruction and total gastrectomy with Roux-en-Y reconstruction. The primary results were Early-phase complications(Anastomotic leakage, Anastomotic bleeding, Abdominal abscess, Abdominal infection, Pulmonary infection, Incision infection, Intestinal obstruction, Dumping syndrome, Pancreatic fistula), Late-phase complications(Intestinal obstruction, Anastomosis stricture, Dumping syndrome, Reoperation, Internal hernia, Incidence of endoscopic gastroesophageal reflux), Serious complications (≥ Grade III C-D score), Quality of life[Gastroesophageal reflux symptom evaluation (Visick score)(≥ III), Los Angeles classification(C or D)], Nutritional status(Hemoglobin, Receipt of vitamin B12 supplementation), Oncologic Outcomes(The 5-year overall survival rates). Secondary outcomes were surgical outcomes (Operative time, Estimated blood loss, Postoperative hospital stay, Number of harvested lymph nodes, Gas-passing, Postoperative mortality).The Cochrane risk-of-bias tool and Newcastle‒Ottawa scale were used to assess the quality of the included studies. RESULTS: After screening, 11 studies were finally included, including 1154 patients. Results from the combined literature showed that total gastrectomy had a significant advantage over proximal gastrectomy with double-tract reconstruction in mean operating time (MD = 4.92, 95% CI: 0.22∼9.61 P = 0.04). However, meta-analysis results showed that Hemoglobin (MD = 7.12, 95% CI:2.40∼11.84, P = 0.003) and Receipt of vitamin B12 supplementation (OR = 0.12, 95% CI:0.05∼0.26, P < 0.00001) in the proximal gastrectomy with double-tract reconstruction group were better than those in the total gastrectomy with Roux-en-Y reconstruction group. There is no significant difference between the proximal gastrectomy with double-tract reconstruction and the total gastrectomy with Roux-en-Y reconstruction group in Early-phase complications(OR = 1.14,95% CI:0.79∼1.64, P = 0.50), Late-phase complications(OR = 1.37,95% CI:0.78∼2.39, P = 0.27), Gastroesophageal reflux symptom evaluation (Visick score)(≥ III)(OR = 0.94,95% CI:0.14∼1.07 P = 0.07), Los Angeles classification(C or D)(OR = 0.33,95% CI:0.01∼8.21, P = 0.50), the 5-year overall survival rates (HR = 1.01, 95% CI: 0.83 ~ 1.23, P = 0.89). CONCLUSION: Proximal gastrectomy with double-tract anastomosis is a safe and feasible treatment for upper gastric carcinoma. However, the operating time was slightly longer in the proximal gastrectomy with double-tract group compared to the total gastrectomy with Roux-en-Y group. The two groups were comparable to the total gastrectomy with Roux-en-Y group in terms of serious complications (≥ Grade III C-D score), early-phase complications, late-phase complications, and quality of life. Although the scope of proximal gastrectomy is smaller than that of total gastrectomy, it does not affect the 5-year survival rate, indicating good tumor outcomes for patients. Compared to total gastrectomy with Roux-en-Y group, proximal gastrectomy with double-tract reconstruction had higher hemoglobin levels, lower probability of vitamin B12 supplementation, and better long-term efficacy. In conclusion, proximal gastrectomy with double-tract reconstruction is considered one of the more rational surgical approaches for upper gastric cancer.

SH3 domain-binding kinase 1 promotes proliferation and inhibits apoptosis of cervical cancer via activating the Wnt/ß-catenin and Raf/ERK1/2 signaling pathways.

SH3 domain-binding kinase 1 (SBK1), is a member of the serine/threonine protein kinases family, and was confirmed to be upregulated in cervical cancer in our previous study. Nonetheless, the role of SBK1 in regulating cancer occurrence and development is unclear. In this study, the stable SBK1-knockdown and -overexpressed cell models were constructed by plasmid transfection technology. Cell viability and growth were assessed through CCK-8, colony formation, and BrdU methods. Cell cycle and apoptosis were analyzed by flow cytometry. The JC-1 staining assay was used to explore mitochondrial membrane potential. The scratch and Transwell assays were used to evaluate the cell metastatic ability. The nude mice models were utilized to explore the SBK1 expression affecting tumor growth in vivo. Our research indicated a high expression of SBK1 both in tissues and cells of cervical cancer. The proliferative, migratory, as well as invasive capacities of cervical cancer cells, were suppressed, and apoptosis was enhanced after SBK1 silence, whereas SBK1 upregulation led to opposite results. In addition, Wnt/ß-catenin and Raf/ERK1/2 pathways were activated by SBK1 upregulation. Furthermore, downregulation of c-Raf or ß-catenin, reversed the proliferation promotion and apoptosis inhibition effects in SBK1-overexpressed cells. The same results were observed with the use of the specific Raf inhibitor. SBK1 overexpression also contributed to tumor growth in vivo. Overall, SBK1 played a vital role in cervical tumorigenesis via activating the Wnt/ß-catenin and Raf/ERK1/2 pathways.

Short- and long-term outcomes of single-port versus multiport laparoscopic radical gastrectomy for gastric cancer: a meta-analysis of propensity score-matched studies and randomized controlled trials.

BACKGROUND: At present, there is no convincing evidence-based medical basis for the efficacy of single-port laparoscopic gastrectomy. To make a high-quality comparison of the short- and long-term outcomes of single-port laparoscopic gastrectomy versus multiport laparoscopic gastrectomy, we performed this meta-analysis, which only included propensity score-matched studies and randomized controlled trials comparing single-port laparoscopic gastrectomy with multiport laparoscopic gastrectomy for patients with gastric cancer. METHODS: Data were retrieved from the electronic databases PubMed, EMBASE, Medline, Cochrane Library, CNKI, Wanfang and VIP up to January 2023, and the data included the outcomes of treatment after single-port laparoscopic gastrectomy and multiport laparoscopic gastrectomy. The primary outcomes were early complications, survival rate after surgery at 1 year, and survival rate after surgery at 5 years. The secondary outcomes were number of pain medications, mean operation time, estimated blood loss, hospital mortality, time to first soft fluid diet, time to first flatus, hospital stay after surgery, and retrieved number of lymph nodes. The Jadad score and Newcastle‒Ottawa scale were used to assess the quality of the included studies. RESULTS: After screening, 9 studies were finally included, including 988 patients. The meta-analysis results showed that estimated blood loss (MD=-29.35, 95% CI: -42.95-15.75, P < 0.0001), hospital stay (MD=-0.99, 95% CI:-1.82~-0.17, P = 0.02), and number of pain medications(MD=-0.65, 95% CI:-1.07~-0.23, P = 0.002) in the single-port laparoscopic gastrectomy group were better than those in the multiport laparoscopic gastrectomy group. There is no significant difference between the single-port laparoscopic gastrectomy group and the multiport laparoscopic gastrectomy group in mean operation time(MD = 5.23,95% CI:-16.58~27.04,P = 0.64), time to first soft fluid diet(MD=-0.06,95% CI: -0.30~0.18,P = 0.63), time to first flatus(MD=-0.18,95% CI:-0.43~0.07,P = 0.16), early complication(OR = 0.73,95% CI:0.50~1.09,P = 0.12), hospital mortality(OR = 1.00,95% CI:0.09~11.16,P = 1.00), retrieved number of lymph nodes(MD=-1.15, 95% CI:-2.71~0.40, P = 0.15), survival rate after surgery 1 year(OR = 2.14,95% CI:0.50~9.07,P = 0.30), and survival rate after surgery 5 year(93.7 vs. 87.6%; p = 0.689). CONCLUSION: This meta-analysis showed that single-port laparoscopic gastrectomy is both safe and feasible for laparoscopic radical gastrectomy for gastric cancer, with similar operation times and better short-term outcomes than multiport laparoscopic gastrectomy in terms of hospital stay, postoperative pain, and estimated blood loss. There was no significant difference in long-term outcomes between single-port laparoscopic gastrectomy and multiport laparoscopic gastrectomy.

A Temperature Independent Inclinometer Based on a Tapered Fiber Bragg Grating in a Fiber Ring Laser.

We demonstrate a new concept for an all-fiber inclinometer based on a tapered fiber Bragg grating (tFBG) in a fiber ring laser (FRL) with the capability of measuring the tilt angle and temperature simultaneously. The sensor performance is analyzed theoretically and investigated experimentally. The dependence of tilt angle on the spectral response in variable temperature conditions was measured. Two inclinometers with different lengths have been fabricated and characterized in FRL. The sensitivity is 0.583 dB/° and 0.849 dB/°, respectively, in the range of 0° to 90°. Thanks to the FRL system, narrow 3-dB bandwidth (<0.1 nm) and high optical signal-to-noise ratio (~60 dB) are achieved. The tFBG in the FRL system can be used for working as a temperature insensitive inclinometer. The results suggested that the proposed inclinometer has the advantages of compact size and convenient manufacture, enhancing its potential for application prospect.

Identification and characterization of interferon regulatory factor 1 from Lateolabrax japonicus involved in antiviral immune response against grouper nervous necrosis virus infection.

Interferon regulatory factors (IRFs) play a key role in mediating the host response against pathogen infection and other important biological processes. In the present study, an interferon regulation factor 1 gene was identified from Lateolabrax japonicus (designated LjIRF-1), the cDNA sequence of LjIRF-1 was 1394 bp long, and with an open reading frame (ORF) of 945 bp that encodes a peptide of 314 amino acids. Bioinformatics data showed that LjIRF-1 possesses a DNA-binding domain (DBD) and two low complexity regions, which shared 56-81% identity to other fish IRF-1s. The LjIRF-1 transcripts were detectable in all examined tissues of healthy L. japonicus, with higher levels in the blood, head-kidney, intestine, gill and spleen. When challenged with grouper nervous necrosis virus (GNNV) and poly (I:C) infection, both the mRNA expression levels of LjIRF-1 and L. japonicus interferon-1 gene (designated LjIFN-1) were significantly up-regulated. Furthermore, like with poly (I:C), the active purified recombinant protein (rLjIRF-1) was also capable of increasing the expression level of LjIFN-1; controlling the copy number of GNNV under lethiferous titer (1011-1012 copies/µL) and promoting the survival rate of GNNV infected L. japonicas. Combine all the results, we deduced that LjIRF-1 is involved in defending GNNV infection by simulating LjIFN-1 signal pathway in L. japonicas.

Modified Hotz Procedure Combined With Modified Z-Epicanthoplasty Versus Modified Hotz Procedure Alone for Epiblepharon Repair.

PURPOSE: To compare the outcomes of the modified Hotz procedure alone and combined with modified Z-epicanthoplasty for correction of epiblepharon. METHODS: Seventy-one Chinese patients who underwent epiblepharon repair were divided into 2 groups. In group 1, 33 patients (59 eyes) were operated on with the modified Hotz procedure. In group 2, 38 patients (71 eyes) were operated on with the modified Hotz procedure combined with modified Z-epicanthoplasty. Treatment outcomes were classified as "excellent" with no cilium-ocular surface touching, "fair" with 5 or fewer cilia-ocular surface touchings, and "poor" with more than 5 cilia-ocular surface touchings. Incision scars were evaluated by the Vancouver scar scale (VSS). RESULTS: There were no significant differences in the age or sex distribution between the two groups. For group 1, the outcome was excellent for 46 eyes (78%) and fair or poor for 13 eyes (22%). For group 2, the outcome was excellent for 70 eyes (98.6%) and fair for only 1 eye (1.4%). Thus, group 2 had significantly more excellent outcomes compared with group 1 (p < 0.001). The Vancouver scar scale of the lower eyelids in group 1 was 1.10 ± 0.30 and 1.04 ± 0.20 in group 2 after correcting for the follow-up period (p = 0.292). The medial canthus Vancouver scar scale in group 2 was 1.13 ± 0.37, which was not different from the lower eyelid Vancouver scar scale (p = 0.471). CONCLUSIONS: The modified Hotz procedure combined with modified Z-epicanthoplasty is more effective in correcting lower eyelid epiblepharon than the modified Hotz procedure alone. The combined procedure does not produce obvious lower eyelid or medial canthus scars.

Neovascular glaucoma: a retrospective review from a tertiary center in China.

BACKGROUND: The purpose of this study is to report the prevalence, etiology, treatment and outcomes of neovascular glaucoma (NVG) in a tertiary care ophthalmic center in China. METHODS: Medical records of patients diagnosed as NVG at the Wenzhou Medical University between 2003 and 2014 were reviewed. Success was defined as IOP between 6 and 21 mmHg without topical or systemic glaucoma medications with retention of presenting visual acuity (VA). RESULTS: NVG was diagnosed in 483 of 8306 (5.8%) of all glaucoma patients. Etiology is reported for all 310 eyes of 284 patients managed in the department. Interventions depended on insurance as well as personal finances; outcomes are reported for the 149 eyes of 138 patients with complete data that met follow up requirements. Diabetic retinopathy (DR,39.7%) was the major cause of NVG. Kaplan Meier survival analysis showed a success rate of 84.8% at 1 year, 47.5% at 3 years and 21.9% at 5 years. Major interventions included glaucoma drainage device (GDD) in 103 eyes and trans-scleral cyclophotocoagulation (TSCPC) in 22 eyes. Complications were more common in the GDD group. CONCLUSIONS: NVG comprised 5.8% of glaucoma patients seen in a tertiary Chinese hospital. DR was identified as the commonest cause and probably reflects the increasing prevalence of diabetes in China. Surgical interventions were partly determined by insurance status and personal finances. GDD was the commonest surgical intervention used and also had the most complications.

Evaluation of the automated urine particle analyzer UF-1000i screening for urinary tract infection in nonpregnant women.

BACKGROUND: Urinary tract infection (UTI) is a widespread disease in women. Urine culture is still the "gold standard" diagnostic test for UTI, but most of them are negative. To reduce unnecessary culture, we evaluated the automated urine particle analyzer UF-1000i screening for UTI in nonpregnant women. METHODS: The urine specimens submitted to our laboratory were submitted for culture and tested by the Sysmex UF-1000i. Bacteria and white blood cell (WBC) counts were compared to standard urine culture results to assess the best cutoff values. RESULTS: In this study, 272 urine samples were included, of which 98 (36.0%) were culture positive with a bacterial cutoff value of 10 x 10(5) CFU/mL. A combination of bacterial (> 95/microL) and/or WBC count (> 24/microL) provided the best screening for UTI, with a sensitivity of 0.99 and a specificity of 0.82 compared with the urine culture. CONCLUSIONS: Sysmex UF-1000i could be used as a screening test for UTI in nonpregnant women. According to the distribution and range of the bacterial scattergram, we could primarily identify and differentiate between Gram-negative and Gram-positive bacteria.

Navigating the personal carbon inclusion scheme: An evolutionary game theory approach to low-carbon behaviors among socio-economic groups.

In response to the challenges posed by climate change, China has launched the Personal Carbon Inclusion (PCI) scheme to encourage individuals to transition towards low-carbon lifestyles. This study investigates the behaviors of participants within the PCI scheme using a tripartite evolutionary game model, encompassing high-income and low-income individuals, as well as the PCI platform itself. The research analyzes participants' strategies, examines the evolutionary stability of different strategies, and assesses the robustness of equilibrium points within the game dynamics. Key findings reveal: (1) High-income participants tend to be less willing to adopt low-carbon behaviors compared to low-income participants. (2) The PCI platform displays limited proactive engagement in promoting low-carbon policies. (3) Factors, particularly the cost and pricing mechanisms of low-carbon actions, significantly impact the evolutionary progression of the system. Moreover, practical recommendations are provided to enhance the effectiveness of PCI schemes.

CMIP6 ESMs overestimate greening and the photosynthesis trends in Dryland East Asia.

The Dryland East Asia (DEA) is one of the largest inland arid regions, and vegetation is very sensitive to climate change. The complex environment in DEA with defects of modeling construction make it difficult to simulate and predict changes in vegetation structure and productivity. Here, we use the emergent constraint (EC) method to constrain the future interannual leaf area index (LAI) and gross primary productivity (GPP) trends in DEA, under four scenarios of the latest Sixth Coupled Model Intercomparison Project (CMIP6) model ensemble. LAI and GPP increase in all scenarios in the near term (2015-2050), with continued growth in SSP370 and SSP585 and stasis in SSP126 and SSP245 in the far term (2051-2100). However, after building effective EC relationships, the constrained increasing trends of LAI (GPP) are reduced by 43.5 %-53.9 % (30.5 %-50.0 %) compared with the uncertainties of the original ensemble, which are reduced by 10.0 %-45.7 % (4.6 %-34.3 %). We also extend the EC in moving windows and grid cells, further strengthening the robustness of the constraints, especially by illustrating spatial sources of these emergent relationships. Overestimations of LAI and GPP trends suggest that current CMIP6 models may be insufficient to capture the complex relationships between climate change and vegetation dynamics in DEA; however, these models can be adjusted based on established emergent relationships.

M1 macrophage-membrane-cloaked paclitaxel/ß-elemene nanoparticles targeting cervical cancer for enhanced therapy.

Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. ß-elemene (ß-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/ß-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/ß-ELE) for co-delivery of PTX&ß-ELE. Through both in vitro and in vivo cervical cancer models, we demonstrated that M1@PLGA/PTX/ß-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/ß-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.

Long-Term outcomes of uncut roux-en-Y anastomosis in laparoscopic distal gastrectomy: A retrospective analysis.

Background: Uncut Roux-en-Y (U-RY) has been increasingly used in radical gastric cancer surgery, but it is still in the exploratory stage. There is insufficient evidence for its long-term efficacy. Methods: From January 2012 to October 2017, a total of 280 patients diagnosed with gastric cancer were eventually included in this study. Patients undergoing U-RY were assigned to the U-RY group, while patients undergoing BillrothII with Braun (B II + Braun) were assigned to the B II + Braun group. Results: There were no significant differences between the two groups in operative time, intraoperative blood loss, postoperative complications, first exhaust time, time to liquid diet, and length of postoperative hospital stay (all P > 0.05). Endoscopic evaluation was performed 1 year after surgery. Compared to B II + Braun group, the uncut Roux-en-Y group had significantly lower incidences of gastric stasis [16.3% (15/92) vs. 28.2% (42/149), χ 2 = 4.448, P = 0.035], gastritis [13.0% (12/92) vs. 24.8% (37/149), χ 2 = 4.880, P = 0.027] and bile reflux [2.2% (2/92) vs. 20.8% (11/149), χ 2 = 16.707, P < 0.001], and the differences were statistically significant. The questionnaire was completed 1 year after surgery,the QLQ-STO22 scores showed that, the uncut Roux-en-Y group had a lower pain score(8.5 ± 11.1 vs. 11.9 ± 9.7, P = 0.009) and reflux score(7.9 ± 8.5 vs. 11.0 ± 11.5, P = 0.012), and the differences were statistically significant (P < 0.05). However, there was no significant difference in overall survival (P = 0.688) and disease-free survival (P = 0.505) between the two groups. Conclusion: Uncut Roux-en-Y has the advantages of better safety, better quality of life and fewer complications, and is expected to be one of the best methods for digestive tract reconstruction.

Evaluation of Duck Egg Hatching Characteristics with a Lightweight Multi-Target Detection Method.

Since it is difficult to accurately identify the fertilization and infertility status of multiple duck eggs on an incubation tray, and due to the lack of easy-to-deploy detection models, a novel lightweight detection architecture (LDA) based on the YOLOX-Tiny framework is proposed in this paper to identify sterile duck eggs with the aim of reducing model deployment requirements and improving detection accuracy. Specifically, the method acquires duck egg images through an acquisition device and augments the dataset using rotation, symmetry, and contrast enhancement methods. Then, the traditional convolution is replaced by a depth-wise separable convolution with a smaller number of parameters, while a new CSP structure and backbone network structure are used to reduce the number of parameters of the model. Finally, to improve the accuracy of the network, the method includes an attention mechanism after the backbone network and uses the cosine annealing algorithm in training. An experiment was conducted on 2111 duck eggs, and 6488 duck egg images were obtained after data augmentation. In the test set of 326 duck egg images, the mean average precision (mAP) of the method in this paper was 99.74%, which was better than the 94.92% of the YOLOX-Tiny network before improvement, and better than the reported prediction accuracy of 92.06%. The number of model parameters was only 1.93 M, which was better than the 5.03 M of the YOLOX-Tiny network. Further, by analyzing the concurrent detection of single 3 × 5, 5 × 7 and 7 × 9 grids, the algorithm achieved a single detection number of 7 × 9 = 63 eggs. The method proposed in this paper significantly improves the efficiency and detection accuracy of single-step detection of breeder duck eggs, reduces the network size, and provides a suitable method for identifying sterile duck eggs on hatching egg trays. Therefore, the method has good application prospects.

Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study.

Introduction: Previous research has reported that the gut microbiota performs an essential role in sleep through the microbiome-gut-brain axis. However, the causal association between gut microbiota and sleep remains undetermined. Methods: We performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression. Results: In forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis. Discussion: In conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.

Fermented Astragalus membranaceus could promote the liver and intestinal health of juvenile tiger grouper (Epinephelus fuscoguttatus).

In order to understand the effects of fermented Astragalus membranaceus (FAM) on the liver and intestinal health of tiger grouper (Epinephelus fuscoguttatus), this study was conducted. This study evaluates the effects of different levels of FAM on liver and intestinal tissue structure, serum biochemical parameters, intestinal digestive enzyme, and microbiota structure of tiger grouper. Fish were fed with diets (crude protein ≥ 48.0%, crude fat ≥ 10.0%) with five levels of FAM (L1:0.25%, L2: 0.5%, L3: 1%, L4: 2% and L5: 4%) in the experimental groups and a regular diet was used as the control (L0: 0%) for 8 weeks. Compared with AM, the protein content of FAM was significantly changed by 34.70%, indicating that a large amount of bacterial protein was produced after AM fermentation, and its nutritional value was improved. FAM had significant effects on the growth performance of tiger grouper (p < 0.05). The high-density lipoprotein cholesterol (HDL-C) was highest in L4 group, being significantly different from L0 group. The area and diameter of hepatocytes were lowest in L3 and L4, and the density of hepatocyte was highest in L4 group and relatively decreased in L5 group. The mucosal height and muscular thickness were highest in L3 group. The intestinal microbiota structure of tiger grouper was changed under the intervention of FAM. The lower abundance of potential pathogenic bacteria and higher abundance of probiotics colonization in the L4 group showed that the dose of FAM had the best effect on improving the health of intestinal microbiota. This study indicates that the addition of FAM in the feed contributes to liver health, improves intestinal morphology, and regulates the intestinal microbiota of tiger grouper. The addition ratio of 1%-2% is better for intestinal and liver health, and a high addition ratio will cause liver damage. Our work will provide a reference for the addition and management of FAM in the aquaculture industry.

Relationship between acrylamide and glycidamide hemoglobin adduct levels and osteoarthritis: a NHANES analysis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and acrylamide is a chemical produced when foods are processed at high temperatures. Recent epidemiological research linked acrylamide exposure from the diet and environment to a number of medical disorders. However, whether acrylamide exposure is associated with OA is still uncertain. This study was aimed at assessing the relationship between OA and hemoglobin adducts of acrylamide and its metabolite glycidamide (HbAA and HbGA). Data were taken from four cycles of the US NHANES database (2003-2004, 2005-2006, 2013-2014, 2015-2016). Individuals aged between 40 and 84 years who had complete information on arthritic status as well as HbAA and HbGA levels were eligible for inclusion. Univariate and multivariate logistic regression analysis s was performed to determine associations between study variables and OA. Restricted cubic splines (RCS) were used to examine non-linear associations between the acrylamide hemoglobin biomarkers and prevalent OA. A total of 5314 individuals were included and 954 (18%) had OA. After adjusting for relevant confounders, the highest quartiles (vs. lowest) of HbAA (adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI), 0.63-1.21), HbGA (aOR = 0.82, 95% CI, 0.60-1.12), HbAA + HbGA (aOR = 0.86, 95% CI, 0.63-1.19), and HbGA/HbAA (aOR = 0.88, 95% CI, 0.63--1.25) were not significantly associated with greater odds for OA. RCS analysis revealed that HbAA, HbGA, and HbAA + HbGA levels were non-linearly and inversely associated with OA (p for non-linearity < 0.001). However, the HbGA/HbAA ratio displayed a U-shaped relationship with prevalent OA. In conclusion, acrylamide hemoglobin biomarkers are non-linearly associated with prevalent OA in a general US population. These findings implicate ongoing public health concerns for widespread exposure to acrylamide. Further studies are still warranted to address the causality and biologic mechanisms underlying the association.

PRAME Promotes Cervical Cancer Proliferation and Migration via Wnt/ß-Catenin Pathway Regulation.

A significant burden is placed on the lives of females due to cervical cancer, which is currently the leading cause of cancer death among women. Preferentially expressed antigen in melanoma (PRAME) belongs to the CTA gene family and was found to be abnormally expressed among different types of cancers. Our previous research also indicated that PRAME was highly expressed in cervical cancer compared with normal tissues. However, the roles and detailed mechanisms of PRAME have not been explored in cervical cancer. In the present study, the expression of PRAME in cervical tissues and cells was detected by immunohistochemistry (IHC), qRT-PCR, and Western blotting. Additionally, CCK-8, BrdU, scratch, transwell, and flow cytometry assays were conducted to explore the function of PRAME in regulating the malignant biological behaviors of cervical cancer cells. Nude mice were used to confirm the role of PRAME in tumor growth in vivo. Furthermore, the Wnt inhibitor MSAB was used to verify the role of PRAME in regulating the Wnt/ß-catenin pathway both in vitro and in vivo. The results of IHC, qRT-PCR, and Western blotting showed that PRAME was highly expressed in cervical cancer tissues and cells. PRAME knockdown attenuated cell growth, migration, and invasion; induced G0/G1 arrest; and increased cell apoptosis in C33A and SiHa cells through Wnt/ß-catenin signaling regulation. However, the upregulation of PRAME exhibited the opposite effects accordingly, which could be partly reversed via MSAB treatment. The growth rate of xenograft tumors was enhanced when PRAME was overexpressed via Wnt/ß-catenin signaling activation. Taken together, PRAME is associated with cervical cancer occurrence and progression mediated by Wnt/ß-catenin signaling, suggesting that PRAME might be a factor in manipulating cervical carcinogenesis and a potential therapeutic target.

Melatonin attenuates lipopolysaccharide-induced immune dysfunction in dendritic cells.

Melatonin, a ubiquitous hormone, is principally secreted from pineal gland in mammals and possesses strong antioxidant and anti-inflammatory properties. However, its specific roles in the immune functions of dendritic cells (DCs) during acute lung injury (ALI) remain unknown. In this study, we found that melatonin restored the body weight, decreased the lung weight/body weight ratio, alleviated the histopathological lung injury, and decreased the levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-12p70, IL-17, and IL-10) in bronchoalveolar lavage fluid of the lipopolysaccharide (LPS)-induced ALI murine model. Moreover, melatonin inhibited the major histocompatibility complex II (MHCII) expression of lung CD11b+ DCs after LPS challenge in vivo. In vitro, melatonin reversed the shape index, promoted the endocytosis, and inhibited phenotypic expression of MHCII, CD40, CD80, and CD86 in LPS-activated DCs. Furthermore, melatonin decreased the expression of an activated marker, CD69, and the secretion of pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-17) after LPS challenge. It hampered the LPS-activated DCs migration by downregulating the C-C chemokine receptor 7 (CCR7) expression, and then weakened the ability of LPS-induced DCs to stimulate allogeneic CD4+ T cell proliferation. Melatonin shaped the immune function of DCs in a nuclear factor erythroid-2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) axis-dependent manner. These findings indicate that melatonin protects DCs from ALI-induced immunological stress and may be used to develop novel DC-targeting strategies for ALI therapy.

Single-cell analysis reveals exosome-associated biomarkers for prognostic prediction and immunotherapy in lung adenocarcinoma.

BACKGROUND: Exosomes play a crucial role in tumor initiation and progression, yet the precise involvement of exosome-related genes (ERGs) in lung adenocarcinoma (LUAD) remains unclear. METHODS: We conducted a comprehensive investigation of ERGs within the tumor microenvironment (TME) of LUAD using single-cell RNA sequencing (scRNA-seq) analysis. Multiple scoring methods were employed to assess exosome activity (EA). Differences in cell communication were examined between high and low EA groups, utilizing the "CellChat" R package. Subsequently, we leveraged multiple bulk RNA-seq datasets to develop and validate exosome-associated signatures (EAS), enabling a multifaceted exploration of prognosis and immunotherapy outcomes between high- and low-risk groups. RESULTS: In the LUAD TME, epithelial cells demonstrated the highest EA, with even more elevated levels observed in advanced LUAD epithelial cells. The high-EA group exhibited enhanced intercellular interactions. EAS were established through the analysis of multiple bulk RNA-seq datasets. Patients in the high-risk group exhibited poorer overall survival (OS), reduced immune infiltration, and decreased expression of immune checkpoint genes. Finally, we experimentally validated the high expression of SEC61G in LUAD cell lines and demonstrated that knockdown of SEC61G reduced the proliferative capacity of LUAD cells using colony formation assays. CONCLUSION: The integration of single-cell and bulk RNA-seq analyses culminated in the development of the profound and significant EAS, which imparts invaluable insights for the clinical diagnosis and therapeutic management of LUAD patients.

The male and female genomes of golden pompano (Trachinotus ovatus) provide insights into the sex chromosome evolution and rapid growth.

INTRODUCTION: Golden pompano (Trachinotus ovatus) is economically significant important for offshore cage aquaculture in China and Southeast Asian countries. Lack of high-quality genomic data and accurate gene annotations greatly restricts its genetic breeding progress. OBJECTIVES: To decode the mechanisms of sex determination and rapid growth in golden pompano and facilitate the sex- and growth-aimed genetic breeding. METHODS: Genome assemblies of male and female golden pompano were generated using Illumina, PacBio, BioNano, genetic maps and Hi-C sequencing data. Genomic comparisons, whole genome re-sequencing of 202 F1 individuals, QTL mapping and gonadal transcriptomes were used to analyze the sex determining region, sex chromosome evolution, SNP loci, and growth candidate genes. Zebrafish model was used to investigate the functions of growth candidate gene. RESULTS: Female (644.45 Mb) and male (652.12 Mb) genomes of golden pompano were assembled and annotated at the chromosome level. Both genomes are highly conserved and no new or highly differentiated sex chromosomes occur. A 3.5 Mb sex determining region on LG15 was identified, where Hsd17b1, Micall2 and Lmx1a were putative candidates for sex determination. Three SNP loci significantly linked to growth were pinpointed, and a growth-linked gene gpsstr1 was identified by locus BSNP1369 (G â†’ C, 17489695, Chr23). Loss of sstr1a (homologue of gpsstr1) in zebrafish caused growth retardation. CONCLUSION: This study provides insights into sex chromosome evolution, sex determination and rapid growth of golden pompano.