Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity

Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT "browning" and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT "browning" by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases

Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer

A major hindrance in gene therapy trials with adeno-associated virus (AAV) vectors is the presence of neutralizing antibodies (NAbs) that inhibit AAV transduction. In this study, we used directed evolution techniques in vitro and in mouse muscle to select novel NAb escape AAV chimeric capsid mutants in the presence of individual patient serum. AAV mutants isolated in vitro escaped broad patient-specific NAb activity but had poor transduction ability in vivo. AAV mutants isolated in vivo had enhanced NAb evasion from cognate serum and had high muscle transduction ability. More importantly, structural modeling identified a 100 amino acid motif from AAV6 in variable region (VR) III that confers this enhanced muscle tropism. In addition, a predominantly AAV8 capsid beta barrel template with a specific preference for AAV1/AAV9 in VR VII located at threefold symmetry axis facilitates NAb escape. Our data strongly support that chimeric AAV capsids composed of modular and nonoverlapping domains from various serotypes are capable of evading patient-specific NAbs and have enhanced muscle transduction

A case report of para-esophageal bronchogenic cyst with esophageal communication

Abstract Paraesophageal bronchogenic cyst was one of common mediastinal congenital cystic lesions of foregut origin. Because of an intimate embryologic relationship with the esophagus, they were usually found intramural (intramural esophageal bronchogenic cysts) with the local esophageal mucosa being intact and the paraesophageal bronchogenic cysts were rarely communicated with esophageal lumen. We report a case of para-esophageal bronchogenic cyst communicating to the esophageal lumen thorough a pedicle of canal, which looked liked a diverticulum on X-ray. During the operation, a communication of paraesophageal bronchogenic cyst with esophageal was found and the pathology diagnosis were made then. The symptoms of chest pain and dysphagia were relieved immediately after operation. The follow-up was well 2 years after the surgery.</jats:p

Sorghum yield prediction using UAV multispectral imaging and stacking ensemble learning in arid regions

IntroductionFrequent droughts and climate fluctuations pose significant challenges to stabilizing and increasing the yields of drought-tolerant crops like sorghum. Accurate, detailed, and spatially explicit yield predictions are essential for precision irrigation, variable fertilization, and food security assessment.MethodsThis study was conducted in the Lifang dryland experimental area in Jinzhong, Shanxi Province, using a sorghum planting experiment. Multispectral imagery and meteorological data were collected simultaneously using a DJI Mavic 3M UAV during key growth stages (seedling emergence, jointing, flowering, and maturity). A “spectral-meteorological-spatial” three-dimensional prediction framework was developed using eight machine learning algorithms. SHAP values and Partial Dependency Plots were used to assess variable importance.ResultsEnsemble learning algorithms performed best, with the Gradient Boosting model achieving an R2 of 0.9491 and Random Forest reaching 0.9070. SHAP analysis revealed that DVI and NDGI were the most important predictors. The jointing stage contributed most to prediction accuracy (R2 = 0.9454), followed by maturity (R² = 0.9215) and flowering (R2 = 0.9075). Yield spatial distribution ranged from 4,291 to 4,965 kg haR-1, with a global Moran’s I index of 0.5552 indicating moderate positive spatial autocorrelation.DiscussionIntegrating UAV multispectral data with machine learning methods enables efficient sorghum yield prediction, with the jointing stage identified as the optimal monitoring period. This study provides crucial technical support for precision planting and efficient sorghum management in arid regions

The global status and hotspots of research in the field of trans-oral endoscopic thyroidectomy (TOET) from 2008 to 2022

PurposeIn this study, the aim was to comprehensively analyze the current status, hotspots, and trends of trans-oral endoscopic thyroidectomy (TOET) through bibliometric analysis and by presenting the field atlas.MethodsWeb of Science Core Collection database was adopted to screen studies regarding TOET published between January 1, 2008 and August 1, 2022. The evaluation covered the criteria total number of studies, keywords, and contributions from countries/regions, institutions, journals, and authors.ResultsA total of 229 studies were covered. SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES is the largest publication in the field of TOET. The three countries that contributed the most studies were Korea, China, and the USA. The most frequently occurring core keywords in the field of TOET are vestibular approach, outcomes, experience, safety, robotic thyroidectomy, scar, video-assisted thyroidectomy and quality-of-life. The seven clusters were generated in this study: intraoperative monitoring of the laryngeal return nerve (# 0), learning curve (# 1), postoperative quality of life (# 2), central lymph node dissection and safety (# 3), complications (# 4), minimally invasive surgery (# 5), and robotic surgery (# 6).ConclusionThe main research topics in the field of TOET place focuses on learning curves, laryngeal nerve monitoring, carbon dioxide gas bolus, chin nerve injury, surgical complications, and surgical safety. In the future, more academics will focus on the safety of the procedure and reducing complications.

A panel based on three-miRNAs as diagnostic biomarker for prostate cancer

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality.Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs.Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p &lt; 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage

Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage

Engineering and Selection of Shuffled AAV Genomes: A New Strategy for Producing Targeted Biological Nanoparticles

We report a DNA shuffling–based approach for developing cell type–specific vectors through directed evolution. Capsid genomes of adeno-associated virus (AAV) serotypes 1–9 were randomly fragmented and reassembled using PCR to generate a chimeric capsid library. A single infectious clone (chimeric-1829) containing genome fragments from AAV1, 2, 8, and 9 was isolated from an integrin minus hamster melanoma cell line previously shown to have low permissiveness to AAV. Molecular modeling studies suggest that AAV2 contributes to surface loops at the icosahedral threefold axis of symmetry, while AAV1 and 9 contribute to two- and fivefold symmetry interactions, respectively. The C-terminal domain (AAV9) was identified as a critical structural determinant of melanoma tropism through rational mutagenesis. Chimeric-1829 utilizes heparan sulfate as a primary receptor and transduces melanoma cells more efficiently than all serotypes. Further, chimeric-1829 demonstrates altered tropism in rodent skeletal muscle, liver, and brain including nonhuman primates. We determined a unique immunological profile based on neutralizing antibody (NAb) titer and crossreactivity studies strongly supporting isolation of a synthetic laboratory-derived capsid variant. Application of this technology to alternative cell/tissue types using AAV or other viral capsid sequences is likely to yield a new class of biological nanoparticles as vectors for human gene transfer

Two sulfur and nitrogen-rich cobalt–thiacalix[4]arene compounds for the selective mercury removal from aqueous solutions

Two thiacalix[4]arene-based coordination compounds, a {Co24} octahedral coordination cage and a {Co8} cluster, are effective adsorbents towards Hg(ii) and the adsorption capacity of the {Co24} cage compound reaches 330 mg g−1.</p