Single-cell combined with transcriptome sequencing to explore the molecular mechanism of cell communication in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a common, chronic, and progressive lung disease that severely impacts human health and survival. However, the intricate molecular underpinnings of IPF remains elusive. This study aims to delve into the nuanced molecular interplay of cellular interactions in IPF, thereby laying the groundwork for innovative therapeutic approaches in the clinical field of IPF. Sophisticated bioinformatics methods were employed to identify crucial biomarkers essential for the progression of IPF. The GSE122960 single-cell dataset was obtained from the Gene Expression Omnibus (GEO) compendium, and intercellular communication potentialities were scrutinized via CellChat. The random survival forest paradigm was established using the GSE70866 dataset. Quintessential genes were selected through Kaplan-Meier (KM) curves, while immune infiltration examinations, functional enrichment critiques and nomogram paradigms were inaugurated. Analysis of intercellular communication revealed an intimate potential connections between macrophages and various cell types, pinpointing five cardinal genes influencing the trajectory and prognosis of IPF. The nomogram paradigm, sculpted from these seminal genes, exhibits superior predictive prowess. Our research meticulously identified five critical genes, confirming their intimate association with the prognosis, immune infiltration and transcriptional governance of IPF. Interestingly, we discerned these genes' engagement with the EPITHELIAL_MESENCHYMAL_TRANSITION signalling pathway, which may enhance our understanding of the molecular complexity of IPF.

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis.

BACKGROUND: Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear. METHODS: We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson's correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins. RESULTS: Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro. CONCLUSIONS: This study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.

Echovirus 11 infection induces pyroptotic cell death by facilitating NLRP3 inflammasome activation.

Echovirus 11 (ECHO 11) is a positive-strand RNA virus belonging to the genus Enterovirus of the family Picornaviridae. ECHO 11 infections can cause severe inflammatory illnesses in neonates, including severe acute hepatitis with coagulopathy. The activation of NLRP3 inflammasome is important for host defense against invading viruses, which also contributes to viral pathogenicity. However, whether and how ECHO 11 induces NLRP3 inflammasome activation remains unclear. In this study, we isolated a clinical strain of ECHO 11 from stools of an ECHO 11-infected newborn patient with necrotizing hepatitis. This virus shared 99.95% sequence identity with the previously published ECHO 11 sequence. The clinically isolated ECHO 11 can efficiently infect liver cells and strongly induces inflammation. Moreover, we showed that ECHO 11 induced IL-1ß secretion and pyroptosis in cells and mouse bone marrow-derived macrophages (BMDMs). Furthermore, ECHO 11 infection triggered NLRP3 inflammasome activation, as evidenced by cleavages of GSDMD, pro-IL-1ß and pro-caspase-1, and the release of LDH. ECHO 11 2B protein was required for NLRP3 inflammasome activation via interacting with NLRP3 to facilitate the inflammasome complex assembly. In vivo, expression of ECHO 11 2B also activated NLRP3 inflammasome in the murine liver. Besides, 2Bs of multiple EVs can also interact with NLRP3 and induce NLRP3 inflammasome activation. Together, our findings demonstrate a mechanism by which ECHO 11 induces inflammatory responses by activating NLRP3 inflammasome, providing novel insights into the pathogenesis of ECHO 11 infection.

High-level production of Rhodiola rosea characteristic component rosavin from D-glucose and L-arabinose in engineered Escherichia coli.

Rosavin is the characteristic component of Rhodiola rosea L., an important medicinal plant used widely in the world that has been reported to possess multiple biological activities. However, the endangered status of wild Rhodiola has limited the supply of rosavin. In this work, we successfully engineered an Escherichia coli strain to efficiently produce rosavin as an alternative production method. Firstly, cinnamate: CoA ligase from Hypericum calycinum, cinnamoyl-CoA reductase from Lolium perenne, and uridine diphosphate (UDP)-glycosyltransferase (UGT) from Bacillus subtilis (Bs-YjiC) were selected to improve the titer of rosin in E. coli. Subsequently, four UGTs from the UGT91R subfamily were identified to catalyze the formation of rosavin from rosin, with SlUGT91R1 from Solanum lycopersicum showing the highest activity level. Secondly, production of rosavin was achieved for the first time in E. coli by incorporating the SlUGT91R1 and UDP-arabinose pathway, including UDP-glucose dehydrogenase, UDP-xylose synthase, and UDP-xylose 4-epimerase, into the rosin-producing stain, and the titer reached 430.5 ± 91.4 mg/L. Thirdly, a two-step pathway derived from L-arabinose, composed of L-arabinokinase and UDP-sugar pyrophosphorylase, was developed in E. coli to further optimize the supply of the precursor UDP-arabinose. Furthermore, 1203.7 ± 32.1 mg/L of rosavin was produced from D-glucose and L-arabinose using shake-flask fermentation. Finally, the production of rosavin reached 7539.1 ± 228.7 mg/L by fed-batch fermentation in a 5-L bioreactor. Thus, the microbe-based production of rosavin shows great potential for commercialization. This work provides an effective strategy for the biosynthesis of other valuable natural products with arabinose-containing units from D-glucose and L-arabinose.

Ultrasensitive measurement of tactile force based on a PDMS-embedded microfiber Mach-Zehnder interferometer.

This study investigates the utilization of an in-fiber interferometer embedded in polydimethylsiloxane (PDMS) to develop a highly sensitive tactile sensor. The tapered mode-field mismatch structure is more conducive to stimulating strong high order modes to promote the sensitivity of the sensor. Experimental investigations are conducted to study the sensing performance of the sensor, resulting in a sensitivity of 23.636 nm/N and a detection limit of 0.746 mN. The experiments demonstrate that employing fast Fourier transform (FFT) and inverse FFT (IFFT) methods to filter weak high order modes significantly improves the repeatability of the sensor, resulting in a repeatability error of less than 1%.

New strategies to study in depth the metabolic mechanism of astaxanthin biosynthesis in Phaffia rhodozyma.

Astaxanthin, a ketone carotenoid known for its high antioxidant activity, holds significant potential for application in nutraceuticals, aquaculture, and cosmetics. The increasing market demand necessitates a higher production of astaxanthin using Phaffia rhodozyma. Despite extensive research efforts focused on optimizing fermentation conditions, employing mutagenesis treatments, and utilizing genetic engineering technologies to enhance astaxanthin yield in P. rhodozyma, progress in this area remains limited. This review provides a comprehensive summary of the current understanding of rough metabolic pathways, regulatory mechanisms, and preliminary strategies for enhancing astaxanthin yield. However, further investigation is required to fully comprehend the intricate and essential metabolic regulation mechanism underlying astaxanthin synthesis. Specifically, the specific functions of key genes, such as crtYB, crtS, and crtI, need to be explored in detail. Additionally, a thorough understanding of the action mechanism of bifunctional enzymes and alternative splicing products is imperative. Lastly, the regulation of metabolic flux must be thoroughly investigated to reveal the complete pathway of astaxanthin synthesis. To obtain an in-depth mechanism and improve the yield of astaxanthin, this review proposes some frontier methods, including: omics, genome editing, protein structure-activity analysis, and synthetic biology. Moreover, it further elucidates the feasibility of new strategies using these advanced methods in various effectively combined ways to resolve these problems mentioned above. This review provides theory and method for studying the metabolic pathway of astaxanthin in P. rhodozyma and the industrial improvement of astaxanthin, and provides new insights into the flexible combined use of multiple modern advanced biotechnologies.

Increased Fruit and Vegetable Consumption Prevents Dysregulated Immune and Inflammatory Responses in High-Fat Diet-Induced Obese Mice.

BACKGROUND: Obesity is often associated with impaired immune responses, including enlarged spleen, increased inflammation, and impaired T-cell-mediated function, which may lead to increased susceptibility to infections. Bioactive compounds found in various fruits and vegetables (F&V) have been shown to have strong anti-inflammatory effects. However, few prospective studies have examined the effects of F&V on preventing obesity-associated dysregulation of immune and inflammatory responses. OBJECTIVE: The objective of this was to determine the impact of different levels of a mixture of F&V incorporated in a high-fat diet (HFD) on immune function changes in a diet-induced obesity animal model. METHODS: Six-wk-old male C57BL/6J mice were randomly assigned to 1 of 5 groups (n = 12/group): matched low-fat control (LF, 10% kcal fat) or HFD (45% kcal fat) supplemented with 0%, 5%, 10%, or 15% (wt/wt) freeze-dried powder of the most consumed F&V (human equivalent of 0, 3, 5-7, 8-9 servings/d, respectively) for 20 wk. Spleen weight was recorded, and the immunophenotype of splenocytes was evaluated by flow cytometry. Ex vivo splenic lymphocyte proliferation was assessed by thymidine incorporation and serum cytokines concentrations were measured by Meso Scale Discovery. RESULTS: Mice fed the HFD exhibited significantly higher spleen weight, decreased splenic CD8+ lymphocytes, suppressed T lymphocyte proliferation, and reduced serum IL-1ß and IFN-γ concentrations compared with those fed the LF diet. Feeding mice with the HFD supplemented with 10% or 15% F&V restored HFD-associated changes of these affected biomarkers compared with those fed HFD only. Furthermore, a significant correlation was found between immunologic markers and F&V level. CONCLUSIONS: These results suggest that increased consumption of F&V has beneficial effects in preventing HFD-associated dysregulation of immune function.

A molecularly imprinted photoelectrochemical sensor based on an rGO/MoSSe heterojunction for the detection of chlortetracycline.

A reduced graphene oxide/molybdenum selenosulfide (rGO/MoSSe) heterojunction was synthesized, and a molecularly imprinted photoelectrochemical sensor for the detection of chlortetracycline was prepared. MoSSe was grown in situ on rGO by a hydrothermal method to form an rGO/MoSSe heterojunction, which acts as the sensitive film of the sensor. Since rGO can promote electron transfer and effectively inhibit electron-hole recombination, it effectively reduces the recombination probability of electrons and holes and improves the photoelectric efficiency, thus enhancing the detection sensitivity of the PEC sensor. The rGO/MoSSe was immobilized on an FTO electrode, and molecularly imprinted polymers (MIPs) were prepared by electropolymerization on the rGO/MoSSe-modified FTO electrode with chlortetracycline as the template molecule and o-phenylenediamine as the functional monomer, so as to construct a molecularly imprinted photoelectrochemical (MIP-PEC) sensor. The determination of chlortetracycline was realized by the strategy of a "gate-controlled effect", and the detection range of the chlortetracycline concentration was 5.0 × 10-13-5 × 10-9 mol L-1 with a detection limit of 1.57 × 10-13 mol L-1. The sensor has been applied to the determination of chlortetracycline in animal-derived food samples.

Radical alkylation of acrylamides with peroxides to access mono/dialkylated fused N-heterocycles.

A simple mono/dialkylation of acrylamide derivatives was achieved, affording diverse mono/dialkylated benzo[4,5]imidazo[2,1-a]isoquinolines or polycyclic coumarins with good substrate scope. This system used common peroxides as alkylating reagents. Meanwhile, a series of scaled-up reactions and mechanistic explorations well demonstrated the application and reaction process of this cascade system.

Metal-free nitro/azido cyclization of 1-acryloyl-2-cyanoindoles to access NO2/N3-featuring pyrrolo[1,2-a] indolediones.

An H2O/heating or [bis(trifluoroacetoxy)iodo]benzene promoted radical cascade nitro/azide cyclization of 1-acryloyl-2-cyanoindoles with tert-butyl nitrite/azidotrimethylsilane was accomplished, which offered a series of nitro/azide-featuring pyrrolo[1,2-a]indolediones in good yields. Meanwhile, some scale-up experiments and substituent transformations were performed to test the synthetic value. In addition, the corresponding radical intermediates were successfully detected by HRMS to support the possible reaction pathway.

Ultra-high PDCR(>109) of vacuum-UV photodetector based on Al-doped Ga2O3microbelts.

Al-doped Ga2O3microbelts with widths ranging from 20 to 154µm and lengths up to 2 mm were grown using carbothermal reduction. Based on these ultra-wide microbelts, single-microbelt (37µm wide) and double-microbelts(38µm/42µm wide) metal-semiconductor-metal photoconductive ultraviolet (UV) detectors PDs were fabricated and their optoelectronic performances were investigated at Vacuum-UV (VUV) wavelengths of 185 nm. Under irradiation of 185 nm, the Al-doped Ga2O3PD has a very-high photocurrent (Iph) of 192.07µA and extremely low dark current (Id) of 156 fA at 10 V, and presents a ultra-high light-to-dark current ratio of 1.23 × 109. The responsivity (R), external quantum efficiency (EQE), and detectivity (D*) of the double-microbelts detector device were 1920 A W-1, 9.36 × 105%, and 8.6 × 1016Jones, respectively. Since the bandgap of the Al-doped microbelts becomes wider, and the fabricated detector has weaker sensitivity to radiation in the 254/365 nm wavelengths. Compared with the 254 nm and 365 nm UV cases, the devices under 185 nm VUV show the excellent high selectivity ratios of 1.47 × 106and 1.7× 107, respectively. This paper should provide a new insight on the VUV photodetectors utilizing Ga2O3microbelts.

Influence of malnutrition according to the glim criteria on the chemotherapy toxicities in patients with advanced lung cancer.

BACKGROUND: Cancer-associated malnutrition is highly prevalent in advanced lung cancer, and 50% of global cancer-related deaths are attributed to cancer-associated malnutrition. Platinum-containing chemotherapy is the standard treatment for advanced lung cancer. Unfortunately, it can cause exacerbated toxicities, which can also have a negative impact on patient's prognosis and quality of life. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been proposed as the world's first accepted diagnostic criteria for malnutrition. However, the effectiveness of GLIM criteria in predicting chemotherapy toxicities in patients with advanced lung cancer is unclear. The aim of this study was to apply the GLIM criteria to assess the prevalence of pre-treatment diagnosis of malnutrition in patients with advanced non-small cell lung cancer (NSCLC) and to determine the impact of nutritional status on patient's chemotherapy toxicity. METHODS: We conducted a study of hospitalized patients with pathologically and clinically diagnosed advanced NSCLC who presented to our hospital from May 2021 to January 2022. Initially, the Nutritional Risk Screening-2002 (NRS-2002) was used for nutritional risk screening, and nutritional status was assessed using the Scored Patient-Generated Subjective Global Assessment (PG-SGA) and GLIM criteria. Chemotherapy toxicity was assessed and graded according to CTCAE5.0, and chemotherapy efficacy was assessed according to RECIST1.1. Kappa test was used to analyze the agreement between PG-SGA and GLIM criteria. Univariate and multivariate logistic regression analyses were used to determine the relationship between malnutrition and chemotherapy toxicity. RESULTS: A total of 215 patients with advanced NSCLC were evaluated for nutritional status. Most of the patients had normal BMI (61.86%) before the start of treatment, 40% were well-nourished as assessed by the PG-SGA tool, and 51.17% were well-nourished as assessed by GLIM criteria. Consistency analysis showed moderate agreement (Kappa = 0.463, P < 0.001) and their correlation was also moderate (Spearman, rs = 0.475, P < 0.001). The objective response rate (ORR) (P = 0.040) and disease control rate (DCR) (P < 0.001) were significantly lower in malnourished patients diagnosed according to GLIM criteria than in well-nourished patients. Multivariate analysis showed that malnutrition (OR = 1.531,95%CI 0.757-3.009; OR = 6.623,95%CI 1.390-31.567, P = 0.046) diagnosed by GLIM criteria was an independent predictor of chemotherapy toxicity. Conclusions Malnutrition diagnosed by GLIM criteria better predicts toxicity during chemotherapy, determines the degree of clinical benefit of chemotherapy, and may affect patient prognosis.

Effect of group online-based peer support intervention on psychological distress of adolescent and young adult cancer patients: a randomized controlled trial.

PURPOSE: Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. METHODS: A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group (N = 45) received conventional psychological care and treatment, and the experimental group (N = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). RESULTS: Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences (P < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients (P < 0.05), and there was an interaction with intervention factors (P < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention (P < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. CONCLUSIONS: The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).

Biosynthesis of eriodictyol in citrus waster by endowing P450BM3 activity of naringenin hydroxylation.

The flavonoid naringenin is abundantly present in pomelo peels, and the unprocessed naringenin in wastes is not friendly for the environment once discarded directly. Fortunately, the hydroxylated product of eriodictyol from naringenin exhibits remarkable antioxidant and anticancer properties. The P450s was suggested promising for the bioconversion of the flavonoids, but less naturally existed P450s show hydroxylation activity to C3' of the naringenin. By well analyzing the catalytic mechanism and the conformations of the naringenin in P450, we proposed that the intermediate Cmpd I ((porphyrin)Fe = O) is more reasonable as key conformation for the hydrolyzation, and the distance between C3'/C5' of naringenin to the O atom of CmpdI determines the hydroxylating activity for the naringenin. Thus, the "flying kite model" that gradually drags the C-H bond of the substrate to the O atom of CmpdI was put forward for rational design. With ab initio design, we successfully endowed the self-sufficient P450-BM3 hydroxylic activity to naringenin and obtained mutant M5-5, with kcat, Km, and kcat/Km values of 230.45 min-1, 310.48 µM, and 0.742 min-1 µM-1, respectively. Furthermore, the mutant M4186 was screened with kcat/Km of 4.28-fold highly improved than the reported M13. The M4186 also exhibited 62.57% yield of eriodictyol, more suitable for the industrial application. This study provided a theoretical guide for the rational design of P450s to the nonnative compounds. KEY POINTS: •The compound I is proposed as the starting point for the rational design of the P450BM3 •"Flying kite model" is proposed based on the distance between O of Cmpd I and C3'/C5' of naringenin •Mutant M15-5 with 1.6-fold of activity than M13 was obtained by ab initio modification.

FKBP5 deficiency attenuates calcium oxalate kidney stone formation by suppressing cell-crystal adhesion, apoptosis and macrophage M1 polarization via inhibition of NF-κB signaling.

Surgical crushing of stones alone has not addressed the increasing prevalence of kidney stones. A promising strategy is to tackle the kidney damage and crystal aggregation inherent in kidney stones with the appropriate therapeutic target. FKBP prolyl isomerase 5 (FKBP5) is a potential predictor of kidney injury, but its status in calcium oxalate (CaOx) kidney stones is not clear. This study attempted to elucidate the role and mechanism of FKBP5 in CaOx kidney stones. Lentivirus and adeno-associated virus were used to control FKBP5 expression in a CaOx kidney stone model. Transcriptomic sequencing and immunological assays were used to analyze the mechanism of FKBP5 deficiency in CaOx kidney stones. The results showed that FKBP5 deficiency reduced renal tubular epithelial cells (RTEC) apoptosis and promoted cell proliferation by downregulating BOK expression. It also attenuated cell-crystal adhesion by downregulating the expression of CDH4. In addition, it inhibited M1 polarization and chemotaxis of macrophages by suppressing CXCL10 expression in RTEC. Moreover, the above therapeutic effects were exerted by inhibiting the activation of NF-κB signaling. Finally, in vivo experiments showed that FKBP5 deficiency attenuated stone aggregation and kidney injury in mice. In conclusion, this study reveals that FKBP5 deficiency attenuates cell-crystal adhesion, reduces apoptosis, promotes cell proliferation, and inhibits macrophage M1 polarization and chemotaxis by inhibiting NF-κB signaling. This provides a potential therapeutic target for CaOx kidney stones.

Association between dietary diversity, sedentary time outside of work and depressive symptoms among knowledge workers: a multi-center cross-sectional study.

BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.

Mechanism of Takifugu bimaculatus Skin Peptides in Alleviating Hyperglycemia in Rats with Type 2 Diabetic Mellitus Based on Microbiome and Metabolome Analyses.

In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.

WITHDRAWN: Treatment of Adhesive Intestinal Obstruction by Nasogastric Tube Under EnhancedRecovery After Surgery: An Efficacy Analysis.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.

Clinical value of nano-carbon lymphatic tracer for regional lymph node dissections of rectal cancer after neoadjuvant chemoradiotherapy.

OBJECTIVES: Regional lymph node (LN) volume decreases after neoadjuvant therapy, requiring a tracer for more accurate detection. Nano-carbon tracer is a third-generation tracer with several advantages, but its use for LN detection after neoadjuvant chemoradiotherapy for middle and low rectal cancer remains unclear. Therefore, this study investigated the effects and safety of anoscope-guided subrectal injections of nano-carbon suspension in this patient population. METHODS: This study retrospectively reviewed the medical records of 45 patients with middle and low rectal cancer admitted to our institution from March 2019 to March 2022. All patients received preoperative neoadjuvant chemotherapy and radiotherapy and were divided into nano-carbon injection (n = 23; anoscope-guided injections of nano-carbon suspension in the rectal submucosa 2 cm above the dentate line 24 h preoperatively) and control (n = 22; directly underwent surgery) groups. The LN detection and complication rates were compared between the groups. RESULTS: The total and mean numbers of LNs and small LNs and the number of patients with > 12 LNs were significantly higher in the nano-carbon injection group than in the control group. The total number of positive LNs and LN metastasis did not differ between the groups, nor did the anastomotic leakage, bleeding, stenosis, and abscess occurrence rates. CONCLUSIONS: Anoscope-guided nano-carbon lymphatic tracing increased the LN detection rate, caused less trauma, and resulted in fewer postoperative complications than the direct surgical procedure. Thus, it is an effective, safe, and practical method that may improve dissections and the postoperative pathological staging accuracy.

SERS biosensors based on catalytic hairpin self-assembly and hybridization chain reaction cascade signal amplification strategies for ultrasensitive microRNA-21 detection.

A highly sensitive surface-enhanced Raman scattering (SERS) biosensor has been developed for the detection of microRNA-21 (miR-21) using an isothermal enzyme-free cascade amplification method involving catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). The CHA reaction is triggered by the target miR-21, which causes hairpin DNA (C1 and C2) to self-assemble into CHA products. After AgNPs@Capture captures the resulting CHA product, the HCR reaction is started, forming long-stranded DNA on the surface of AgNPs. A strong SERS signal is generated due to the presence of a large amount of the Raman reporter methylene blue (MB) in the vicinity of the SERS "hot spot" on the surface of AgNPs. The monitoring of the SERS signal changes of MB allows for the highly sensitive and specific detection of miR-21. In optimal conditions, the biosensor exhibits a satisfactory linear range and a low detection limit for miR-21 of 42.3 fM. Additionally, this SERS biosensor shows outstanding selectivity and reproducibility. The application of this methodology to clinical blood samples allows for the differentiation of cancer patients from healthy controls. As a result, the CHA-HCR amplification strategy used in this SERS biosensor could be a useful tool for miRNA detection and early cancer screening.