PPARα suppresses low-intensity-noise-induced body weight gain in mice: the activated HPA axis plays an critical role.

BACKGROUND: As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders, endocrine modifications. The relationship among low-intensity noise, obesity and lipid-regulating nuclear factor PPARα is not yet clear. METHODS: In this study, male wild-type (WT) and Pparα-null (KO) mice on a high-fat diet (HFD) were exposed to 75 dB noise for 12 weeks to explore the effect of low-intensity noise on obesity development and the role of PPARα. 3T3-L1 cells were treated with dexamethasone (DEX) and sodium oleate (OA) to verify the down-stream effect of hypothalamic-pituitary-adrenal (HPA) axis activation on the adipose tissues. RESULTS: The average body weight gain (BWG) of WT mice on HFD exposed to noise was inhibited, which was not observed in KO mice. The mass and adipocyte size of adipose tissues accounted for the above difference of BWG tendency. In WT mice on HFD, the adrenocorticotropic hormone level was increased by the noise challenge. The aggravation of fatty liver by noise exposure occurred in both mouse lines, and the transport of hepatic redundant lipid to adipose tissues were similar. The lipid metabolism in adipose tissue driven by HPA axis accorded with the BWG inhibition in vivo, validated in 3T3-L1 adipogenic stem cells. CONCLUSION: Chronic exposure to low-intensity noise aggravated fatty liver in both WT and KO mice. BWG inhibition was observed only in WT mice, which covered up the aggravation of fatty liver by noise exposure. PPARα mediates the activation of HPA axis by noise exposure in mice on HFD. Elevated adrenocorticotropic hormone (ACTH) promoted lipid metabolism in adipocytes, which contributed to the disassociation of BWG and fatty liver development in male WT mice. Summary of PPARα suppresses noise-induced body weight gain in mice on high-fat-diet. Chronic exposure to low-intensity noise exposure inhibited BWG by PPARα-dependent activation of the HPA axis.

Insights of Life Molecules' Dynamic Distribution in Live Cells via Sequence-Structure Bispecific Fluorescent RNA.

Life molecules' distributions in live systems construct the complex dynamic reaction networks, whereas it is still challenging to demonstrate the dynamic distributions of biomolecules in live systems. Herein, we proposed a dynamic analysis strategy via sequence-structure bispecific RNA with state-adjustable molecules to monitor the dynamic concentration and spatiotemporal localization of these biomolecules in live cells based on the new insight of fluorescent RNA (FLRNA) interactions and their mechanism of fluorescence enhancement. Typically, computer-based nucleic acid-molecular docking simulation and molecular theoretical calculation have been proposed to provide a simple and straightforward method for guiding the custom-design of FLRNA. Impressively, a novel FLRNA with sequence and structure bispecific RNA named as a structure-switching aptamer (SSA) was introduced to monitor the real-time concentration and spatiotemporal localization of biomolecules, contributing to a deeper insight of the dynamic monitoring and visualization of biomolecules in live systems.

Three-in-One System Based on Multi-Path Nucleic Acid Amplification for Bioanalysis of Pre-miRNA/miRNA and Dicer Activity.

Today, a lot of attention is being paid to the pre-miRNAs/miRNAs or activity of Dicer due to their important functions in various physiological processes. Especially, the intrinsic relationship among these associated targets is of significant importance for more in-depth research on the mechanism of disease formation and early diagnosis. Herein, a strategy for simultaneous bioanalysis of miRNAs/pre-miRNAs and Dicer enzyme based on the self-designed multi-path nucleic acid amplification technology was proposed. Typically, in the presence of pre-miRNA-155, it can hybridize with Helper to generate a structure with two new toeholds, one of which could react with H1, H2, and H3, performing a modified CHA reaction with obvious fluorescence responses of FAM, and another of which could hybridize with H4, H5, and H6 to construct the [H4-H5-H6]n DNA nanosphere with obvious fluorescence responses of Cy5. Similarly, miRNA-155 could just hybridize with H1, H2, and H3 to generate the same modified CHA reaction with obvious fluorescence responses of FAM. Due to the successful multi-path nucleic acid amplification, the proposed bioanalysis strategy could be successfully employed for miRNA-155 and pre-miRNA-155 analysis in the range from 500 pM to 100 nM and 1 to 300 nM, respectively. The proposed strategy could be applied to explore another inter-related nucleic acid relationship also, providing great potential in bioanalysis of various nucleic acids.

Safety and feasibility of neoadjuvant chemotherapy as a surgical bridge for acute left-sided malignant colorectal obstruction: a retrospective study.

BACKGROUND: For colorectal cancer, preoperative (neoadjuvant) chemotherapy is more effective than postoperative chemotherapy because it not only eradicates micrometastases more effectively but also reduces the risk of incomplete intraoperative resection and tumor cell shedding. For the treatment of acute left-sided malignant colorectal obstruction, colorectal stents as well as stoma are being used to relieve the obstructive colorectal cancer, and as a bridge to surgery, allowing easy mobilization and resection of the colon. Neoadjuvant chemotherapy combined with self-expandable metal stents (SEMS) or neoadjuvant chemotherapy combined with decompressing stoma (DS) can be used as a bridge to elective surgery (BTS) as an alternative to emergency surgery in patients with acute left-sided malignant colorectal obstruction, but its benefit is uncertain. The purpose of this study was to evaluate the safety and feasibility of neoadjuvant chemotherapy as a bridge to surgery in the treatment of acute left-sided malignant colorectal obstruction. METHODS: Data from patients who were admitted with acute left-sided malignant colorectal obstruction between January 2012 and December 2020 were retrospectively reviewed, and patients with gastrointestinal perforation or peritonitis were excluded. We performed one-to-two propensity score matching to compare the stoma requirement, postoperative complications, and other short-term oncological outcomes between the neoadjuvant chemotherapy group and surgery group. RESULTS: There were no differences in intraoperative blood loss, operative time, one-year postoperative mortality, and postoperative tumor markers between the two groups. The 1-year recurrence-free survival (RFS) rates of neoadjuvant chemotherapy group and surgery group were 96.8 and 91.3% (p = 0.562). The neoadjuvant chemotherapy group was able to reduce stoma rate 1 year after surgery (p = 0.047). Besides, the neoadjuvant group significantly reduced postoperative bowel function time (p < 0.001), postoperative hospital stay (p < 0.001), total hospital stay (p = 0.002), postoperative complications (p = 0.017), reduction in need to stay in the intensive care unit (ICU) (p = 0.042). CONCLUSIONS: Neoadjuvant chemotherapy as a bridge to elective surgery in patients with acute left-sided malignant colorectal obstruction is safe and has many advantages. Prospective multicenter studies with large samples are needed to further evaluate the feasibility of neoadjuvant chemotherapy.

Endoscopic management of postoperative anastomotic bleeding in patients with colorectal cancer.

BACKGROUND: Postoperative anastomotic bleeding is considered a rare but life-threatening complication. There is no standard treatment strategy for this emergency condition. The aim of this study was to report our experiences in the management of postoperative anastomotic bleeding in patients with colorectal cancer. METHODS: We analyzed the general characteristics, treatments, and outcomes of patients with anastomotic bleeding after surgery for colorectal carcinoma at the Sixth Affiliated Hospital of Sun Yat-Sen University between July 2013 and September 2019 retrospectively. A univariate and multivariate analysis was performed to find protective factors for endoscopic hemostasis. Risk factors for anastomotic leakage after colonoscopy were also analyzed. RESULTS: A total of 9870 patients underwent surgeries for colorectal carcinoma between July 2013 and September 2019. Colonoscopies were performed in 78 cases with postoperative anastomotic bleeding. The effective rate of initial endoscopic hemostasis was 81% (63/78). In univariate and multivariate analysis, hemoclip therapy (odds ratio = 4.572; 95%CI 1.305-16.017; P = 0.017) and postoperative anastomotic bleeding within 5 days (odds ratio = 3.639; 95%CI 1.045-12.675; P = 0.042) are protective factors for endoscopic hemostasis. Comorbidity was associated with an increased risk for anastomotic leakage. CONCLUSIONS: Colonoscopy seems to be an effective way to achieve hemostasis for patients with anastomotic bleeding after surgery for colorectal carcinoma. It may be more effective in the early postoperative period, and hemoclip appears to be the first choice to control postoperative anastomotic bleeding.

Gastrokine-2 suppresses epithelial mesenchymal transition through PI3K/AKT/GSK3ß signaling in gastric cancer.

Epithelial-mesenchymal transition (EMT) plays an important role in metastasis of gastric cancer. Our previous study showed that Gastrokine-2 (GKN2) can inhibit the metastasis of SGC-7901 and AGS cells. Herein, we further explored the role of GKN2 in epithelial mesenchymal transition of gastric cancer cells and the underlying mechanisms. We found that overexpression of GKN2 can lower the protein expression level of Snail and markedly elevate E-cadherin protein level in SGC7901 and AGS cells. Further data showed that knockdown of snail can inhibit the migration and invasion of SGC-7901 and AGS cells. It is known that Snail can be phosphorylated by GSK3ß, a downstream protein of PI3K/AKT pathway. We then test protein expression of p-GSK3ß(Ser-9), the downstream protein of PI3K/AKT, which was significantly decreased under the circumstance of GKN2 overexpression. Moreover, LY294002, a PI3K inhibitor, can reverse the protein expression change of E-cadherin and snail induced by siGKN2. Taken together, these findings suggested that GKN2 suppressed epithelial mesenchymal transition of gastric cancer cells by downregulation of snail through PI3K/AKT/GSK3ß signaling pathway.

Effect of circadian rhythm change on gut microbiota and the development of nonalcoholic fatty liver disease in mice.

BACKGROUND: This study was to investigate the effect and possible mechanism of circadian rhythm change on the development of nonalcoholic fatty liver disease (NAFLD) in mice. METHODS: A total of 80 male SPF-grade 4-week C57BL/6J mice were randomly divided into normal diet normal light/dark cycle (ND-LD) and high-fat diet all dark (HFD-DD) groups. Weight measurements were taken weekly, and after 24 weeks of intervention, 24 mice from both groups were randomly selected and analyzed. Additionally, the remaining mice in the HFD-DD group were divided into two groups: one group continued the high-fat all-dark treatment (HFD-DD-DD), and the other group was restored to normal light/dark cycle treatment (HFD-DD-LD). Mice were euthanized after a total of 48 weeks of intervention. Measurements were taken for each mouse including liver function serum indicators, liver tissue pathological sections, rhythm-related proteins, and determination of the gut microbiota community. RESULTS: The HFD induced NAFLD in mice, exhibiting symptoms such as obesity, lipid and glucose metabolism disorders, elevated liver enzymes, and decreased gut microbiota diversity. The composition of the gut microbiota was significantly different from that of the normal diet group, with a significant increase in the ratio of Firmicutes to Bacteroides. Restoration of normal light/dark cycles exacerbated the disorder of lipid metabolism, liver steatosis, and the expression of BMAL1 in mice and significantly reduced the diversity of gut microbiota. CONCLUSIONS: Circadian rhythm changes aggravate the development of NAFLD induced by a high-fat diet by affecting glucose metabolism, liver steatosis, and gut microbiota diversity. Restoration of normal circadian rhythm did not improve NAFLD. Our findings open up new avenues for the prevention, diagnosis, and treatment of NAFLD.

Synergistic Drug-Loaded Shear-Thinning Star Polymer Hydrogel Facilitates Gastrointestinal Lesion Resection and Promotes Wound Healing.

Easy injection, long-lasting barrier, and drug loading are the critical properties of submucosal injection materials for endoscopic surgery. However, conventional injectable polymers face challenges in simultaneously attaining these properties due to the inherent conflict between injectability and in situ stability. Here, a multi-arm star polymer hydrogel (denoted as ßCP hydrogel) with long-lasting submucosal barrier (exceeding 120 min), rapid hemostasis, and sustained antibacterial properties is successfully developed by grafting poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) side-chains from ß-CD via atom transfer radical polymerization (ATRP). During the onset of shearing, ßCP hydrogel experiences the unwinding of polymer side-chains between neighboring star polymers, which facilitates the process of endoscopic injectability. After submucosal injection, ßCP hydrogel undergoes the winding of polymer side-chains, thereby establishing a long-lasting barrier cushion. Meanwhile, owing to its distinctive structures with a hydrophobic inner cavity and an outer layer of hydrophilic polymer side-chains, ßCP hydrogel enables simultaneous loading and on-demand release of diverse categories of drugs. This unique performance can adapt to the diverse demands during different stages of wound healing in a porcine endoscopic surgery model. These results indicate an appealing prospect for new application of star polymers as a good submucosal injection material in endoscopic treatments.

Depression Exacerbates Hepatic Steatosis in C57BL/6J Mice by Activating the Hypothalamic-Pituitary-Adrenal Axis.

BACKGROUND/AIM: Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known. MATERIALS AND METHODS: In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot. RESULTS: The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses. CONCLUSION: Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them.

Effect of acupuncture at the acupoints for Yizhi Tiaoshen on the functional connectivity between the hippocampus and the brain in the patients with Alzheimer's disease. / 针刺"益智调神"ç©´æ–¹å¯¹é˜¿å°”èŒ¨æµ·é»˜ç— æ‚£è€ æµ·é©¬ä¸Žå ¨è„‘åŠŸèƒ½è¿žæŽ¥çš„å½±å“.

OBJECTIVES: To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen, i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group). RESULTS: After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups (P<0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group (P≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus (P<0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment (P<0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus (P<0.05), and it was declined with the left thalamus (P<0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus (P<0.05) compared with that of the western medication group. CONCLUSIONS: Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.

Effects of Different Preparation Methods on Microbiota Composition of Fecal Suspension.

Fecal microbiota transplantation is an emerging disease-modifying therapy. The viability of the microbiome in feces and its successful transfer depends on the preparation of fecal microbiota suspension. However, currently, no standard operation procedure is proposed for fecal suspension preparation. This study aims to compare the effect of different preparation methods on the composition of fecal microbiota composition in the rat. Four methods were used to collect the fecal suspension from fresh rat fecal (Group A), including stirring with normal saline (Group B), stirring with normal saline and then standing (Group C), stirring with normal saline and filtered with gauze (Group D), and stirring with normal saline and centrifuged (Group E). 16S ribosomal RNA gene (16S rDNA) sequencing technology was used to analyze the microbiota diversity and composition of each group of samples. Compared with fresh feces, the bacterial richness of the fecal suspension obtained by the four methods was significantly decreased (P < 0.05). The structural similarity with fresh fecal microbiota from high to low is groups B, D, C, and E. All four methods changed the microbiota structure to varying degrees, thus may affect the effect of FMT. In conclusion, choosing different methods to prepare fecal suspensions may help to better optimize the application of FMT.

A novel photoelectrochemical strategy for sequence-spot bispecific analysis of N6-methyladenosine modification based on proximity ligation-triggered cascade amplification.

N6-methyladenosine (m6A) modification as the most prevalent mammalian RNA internal modification has been considered as the invasive biomarkers in clinical diagnosis and biological mechanism researches. It is still challenged to explore m6A functions due to technical limitations on base- and location-resolved m6A modification. Herein, we firstly proposed a sequence-spot bispecific photoelectrochemical (PEC) strategy based on in situ hybridization mediated proximity ligation assay for m6A RNA characterization with high sensitivity and accuracy. Firstly, the target m6A methylated RNA could be transferred to the exposed cohesive terminus of H1 based on the special self-designed auxiliary proximity ligation assay (PLA) with sequence-spot bispecific recognition. The exposed cohesive terminus of H1 could furtherly trigger the next catalytic hairpin assembly (CHA) amplification and in situ exponential nonlinear hyperbranched hybridization chain reaction for highly sensitive monitoring of m6A methylated RNA. Compared with conventional technologies, the proposed sequence-spot bispecific PEC strategy for m6A methylation of special RNA based on proximity ligation-triggered in situ nHCR performed improved sensitivity and selectivity with a detection limit of 53 fM, providing new insights into highly sensitive monitoring m6A methylation of RNA in bioassay, disease diagnosis and RNA mechanism.

Identification of disease-related genes and construction of a gene co-expression database in non-alcoholic fatty liver disease.

Background: The mechanism of NAFLD progression remains incompletely understood. Current gene-centric analysis methods lack reproducibility in transcriptomic studies. Methods: A compendium of NAFLD tissue transcriptome datasets was analyzed. Gene co-expression modules were identified in the RNA-seq dataset GSE135251. Module genes were analyzed in the R gProfiler package for functional annotation. Module stability was assessed by sampling. Module reproducibility was analyzed by the ModulePreservation function in the WGCNA package. Analysis of variance (ANOVA) and Student's t-test was used to identify differential modules. The receiver operating characteristic (ROC) curve was used to illustrate the classification performance of modules. Connectivity Map was used to mine potential drugs for NAFLD treatment. Results: Sixteen gene co-expression modules were identified in NAFLD. These modules were associated with multiple functions such as nucleus, translation, transcription factors, vesicle, immune response, mitochondrion, collagen, and sterol biosynthesis. These modules were stable and reproducible in the other 10 datasets. Two modules were positively associated with steatosis and fibrosis and were differentially expressed between non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL). Three modules can efficiently separate control and NAFL. Four modules can separate NAFL and NASH. Two endoplasmic reticulum related modules were both upregulated in NAFL and NASH compared to normal control. Proportions of fibroblasts and M1 macrophages are positively correlated with fibrosis. Two hub genes Aebp1 and Fdft1 may play important roles in fibrosis and steatosis. m6A genes were strongly correlated with the expression of modules. Eight candidate drugs for NAFLD treatment were proposed. Finally, an easy-to-use NAFLD gene co-expression database was developed (available at https://nafld.shinyapps.io/shiny/). Conclusion: Two gene modules show good performance in stratifying NAFLD patients. The modules and hub genes may provide targets for disease treatment.

Analysis of the relationship between the gut microbiota enterotypes and colorectal adenoma.

Introduction: The essence of enterotypes is to stratify the entire human gut microbiota, and dysregulation of gut microbiota is closely related to the development of colorectal adenoma. Enterotypes may therefore be a useful target for the prevention of colorectal adenoma. However, the relationship between gut microbiota and colorectal adenoma has not been fully elucidated. In this study, we aimed to analyze the differences in gut microbiome composition between adenoma and control populations. Methods: We recruited 31 patients with colorectal adenoma and 71 non-adenoma controls. Patient demographics, risk factors, fecal samples from each subject were collected and metagenomic sequencing was performed. LEfSe analysis was used to reveal differences in intestinal microbiome composition. Multiple logistic regression analysis was used to determine the association between enterotypes and colorectal adenoma. Results: The results showed that Prevotella enterotype (enterotype 4) is only present in adenoma group. Logistic regression analysis showed that Prevotella enterotype was an independent risk factor for colorectal adenoma. Discussion: The Prevotella enterotype may increase the occurrence of colorectal adenoma through inflammatory association and interference with glucose and lipid metabolism in human body. In conclusion, the differences we observed between different enterotypes add a new potential factor to the development of colorectal adenoma.

Ultrasensitive quantitation of Paraquat based on a small molecule-induced dual-cycle amplification strategy.

Paraquat (PQ) is a typical biotoxic small molecule. Knowledge of how to directly introduce it into cyclic amplification rather than transform it into a secondary target is lacking in current analytical methods. Considering the urgent need for trace pesticide residue detection and the inherent defects of small molecule analysis, a CRISPR/Cas12a-driven small molecule-induced dual-cycle strategy was developed based on the immune competition method. The key to signal amplification is the mutual activation and acceleration between Cycle 1 triggered by the small molecule and Cycle 2 driven by CRISPR/Cas12a. Impressively, small molecules have been successfully incorporated into the dual-cycle strategy, which achieves a low detection limit (3.1 pg/mL) and a wide linear range (from 10 pg/mL to 50 µg/mL). Moreover, the designed biosensor was successfully employed to evaluate the PQ residual level in real samples and showed effective implementation for the bioanalysis of small molecule targets and pesticide residue-related food safety.

Changes of gut microbiota under different nutritional methods in elderly patients with severe COVID-19 and their relationship with prognosis.

Background: The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes. Results: A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis. Conclusions: This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.

Proximity hybridization-induced competitive rolling circle amplification to construct fluorescent dual-sensor for simultaneous evaluation of glycated and total hemoglobin.

The glycated hemoglobin (HbA1c) level, defined as the ratio of HbA1c to total hemoglobin (tHb), has been considered as a standard index for diabetes mellitus diagnosis, avoiding any short-term fluctuation of the blood glucose level. However, it is still a key challenge that some complicated separation procedures are required to detect HbA1c and tHb in a single experiment. Herein, we developed a dual-sensing fluorescent assay for HbA1c and tHb based on proximity hybridization-induced rolling circle amplification (RCA) and T7 exonuclease aided signal cycle to calculate the HbAlc level in one single experiment. Typically, four DNA-tagged probes were used for immunoreactions of anti-HbA1c antibodies (Ab1) and anti-Hb antibodies (Ab2) with HbA1c and Hb, respectively. The RCA1 and RCA2 were induced by the complexes of assistant DNAs and the products of proximity hybridization with anti-HbA1c-DNA1 (2) and anti-Hb-DNA3 (4), respectively. Meanwhile, the tHb in solution could prevent the existing RCA2 based on its competing with Hb-DNA3 for Ab2-DNA4. Thus, RCA1 and RCA2 routes create "signal-on" and "signal-off" readouts, respectively. After the hybridization of signal probes and RCA products, the quenched fluorescence was recovered by the digestion of T7 exonuclease. Under optimized conditions, the method displayed high sensitivity with a limit of detection 2.17 ng/mL and 33.4 ng/mL for HbA1c and tHb, respectively, and the real sample analysis results were found to match well with the theoretical data, holding feasibility for rapid, homogeneous, and easy HbA1c level evaluation and great promise as a potential alternative tool to analyze HbA1c level clinically.

Choice of injection time of conscious sedation and its impact on pain control in colonoscopy.

Purpose: The aim of this study was to identify the effect of different injection times on pain during colonoscopy procedure. Methods: In this retrospective study, the data of patients who underwent colonoscopy from June 2020 to September 2020 were assessed to investigate the effect of different injection time of sedative drugs (midazolam and dezocine). The primary endpoint was evaluating the pain intensity of the patients using visual analogue scale (VAS) immediately after colonoscopy . Results: A total of 152 patients were eligible for this study. Of them, 76 received midazolam and dezocine injection 1 min prior to the colonoscopy procedure (the 1 Min group) and the other 76 patients received the injection 3 min prior to the procedure (the 3 Min group). The vital signs of all patients were stable except for one patient who was diagnosed with inflammatory bowel disease in the 3 Min group. A transient drop in blood pressure for this patient was observed during colonoscopy but returned to normal after general treatment. The two groups had similar rates of cecal intubation (84.21% vs. 90.97%, P = 0.22), addition of sedative drugs during procedure (2.63% vs. 5.26%, P = 0.68), and adequate bowel preparation (Boston Bowel Preparation Scale ≥6, 61.84% vs. 61.84%, P = 1.0). However, patients in the 3 Min group had significantly lower VAS than those in the 1 Min group [0 (0, 1) vs. 1 (0, 2), P = 0.041]. Conclusion: The timing of drug injection during conscious sedation may affect pain control during colonoscopy, with 3 min prior to the procedure showing lower VAS.