Body mass index and carpal tunnel syndrome: A case-control study.

To investigate the electrophysiological characteristics of carpal tunnel syndrome (CTS) and to evaluate the relationship between electrophysiological indexes and body mass index (BMI). In the analysis of 153 hospitalized patients with CTS, the median motor conduction velocity, motor conduction amplitude, motor conduction latency, sensor conduction velocity, sensor conduction amplitude and median sensory latency were analyzed. BMI was calculated. Total 171 healthy individuals were selected as control group. According to Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults, patients were divided into groups A, B and C. Patients with BMI (kg/m2) <24 were classified into group A; those with 24 ≤ BMI < 28 were regarded as overweight and classified into group B; and those with BMI ≥ 28 were regarded as obese and classified into group C. The BMI of CTS patients was significantly higher than that of healthy individuals (P < .05). For the sensory nerve, with the increase of BMI, the incubation period was gradually prolonged and the conduction velocity gradually decreases (P < .05). In terms of motor latency, with an increase in BMI, the latency showed a trend of first decreasing and then increasing, while the conduction velocity showed a trend of first increasing and then decreasing (P < .05). Electrophysiological examination plays an important supporting role in the diagnosis of CTS. BMI is positively correlated with the degree of CTS injury to a certain extent. Weight loss can effectively prevent the occurrence of CTS and slow the progression of nerve damage in CTS patients.

Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis.

INTRODUCTION: This study aimed to evaluate the clinical efficacy and safety of 4 weekly formulations of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control, including glycemic control, by using a network meta-analysis (NMA). METHODS: PubMed, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched from inception until June 10, 2022. Randomized clinical trials (RCTs) enrolling participants with diabetes mellitus type 2 and a follow-up of at least 12 weeks were included, for which 4 eligible GLP-1RAs Exenatide, Dulaglutide, Semaglutide, Loxenatide were compared with either each other or placebo. The primary outcome is the change of hemoglobin A1c level. Secondary outcomes including additional glycemic control indicators and adverse events (AE). Frequentist random-effect NMA were conducted for effect comparison. This meta-analysis was registered on PROSPERO, CRD42022342241. RESULTS: The NMA synthesized evidence from 12 studies covering 6213 patients and 10 GLP-1RA regimens. A pairwise comparison of glycosylated hemoglobin type A1C (HbA1c) lowering effects showed that once-weekly GLP-1 receptor agonists were significantly better than placebo, and their glucose-lowering intensity was Semaglutide 2.0mg, Semaglutide 1.0mg, Dulaglutide 4.5mg, and Semaglutide 0.5mg, Dulaglutide 3.0mg, PEX168 200ug, Dulaglutide 1.5mg, PEX168 100ug and Dulaglutide 0.75mg. The GLP-1RA regimen has a comparable safety profile for hypoglycemia. And with the exception of PEX168, all other long-acting GLP-1RA drugs had lower rates of diarrhea, nausea and vomiting than placebo. CONCLUSION: Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance.

Pannier is a key regulator of embryogenesis, pupal development and female reproduction in the insect pest Bactrocera dorsalis.

BACKGROUND: Most arthropods are famous for their large reproductive capacity, with the ovary playing a vital role in the process. The study of the regulatory mechanisms of ovarian development may have the potential for a reproduction-based pest management strategy. GATA-binding transcription factors (GATAs) as important regulatory factors mediate many physiological processes, including development, immunity, insecticide resistance and reproduction. The Pannier (pnr), a member of GATA family, was confirmed to be involved in ovarian development of Bactrocera dorsalis in our previous study. However, the direct evidence of pnr regulating the fly ovarian development is still lacking. RESULTS: We used CRISPR/Cas9 to create Bdpnr loss-of-function mutations. Homozygous Bdpnr-/- mutants were nonviable, with most individuals dying during embryogenesis, some surviving to the larval stages, and the remaining few dying during pupation. In contrast, heterozygous individuals reached the adult stage, but ovarian development was disrupted, with concomitant decreases in egg laying and hatching rates. We also found that two genes encoding vitellogenin proteins (BdVg1 and BdVg2) and the vitellogenin receptor (BdVgR) were significantly down-regulated in heterozygous mutants compared to wild-type controls. CONCLUSION: These results indicate that Bdpnr is required for embryonic and post-embryonic development, including the formation of ovaries. Bdpnr could therefore be considered as a molecular target for tephritid fly pest control. © 2022 Society of Chemical Industry.

Impairment of a NIK-SIX Feedback Axis Results in Dysregulation of Intestinal Immune Homeostasis and Promotes Early-onset Fatal Spontaneous Colitis.

BACKGROUND: The negative feedback circuit NIK-SIN could inhibit the systemic inflammation and protect mouse from endotoxic shock. However, the physiological significance of NIK-SIX feedback circuit in the maintenance of intestinal immune homeostasis and prevention of early-onset spontaneous colitis is not known. OBJECTIVE: To explore the role of NIK-SIX axis in the maintenance of intestinal immune homeostasis. METHODS: The conditional knockout of NIK encoding gene, Map3k14, in the Cd11c+ dendritic cells were generated by crossing Map3k14-flox mice with Cd11c-Cre mice. DSS was used for colitis models. The expression of cytokines in the intestinal immune cells, isolated from Map3k14-cKO mice were detected by qPCR. The siRNA molecules were used for the silencing of SIN-proteins. Then luciferase assays and chromatin immunoprecipitation combined with qPCR were applied for mechanism investigations. RESULTS: The expression of SIX1 and SIX2 protein in BMDMs from WT were significantly lower than in the Map3k14-cKO mice. In vitro, the NIK-/- human-derived circulating monocytes also failed to express SIX-proteins under the stimulation of non-canonical NF-κB agonists. The expression of cytokines was significantly decreased in human circulating monocytes with overexpression SIN-proteins. The expression of cytokines in macrophages, DCs and T cells isolated from Map3k14-cKO mice were significantly increased in the DSS-induced models. Higher expression of cytokines was observed in the SIN1-/- and SIN2-/- cells including human circulating monocytes, mouse-derived BMDMs, intestinal macrophages and DCs. SIN-proteins directly bound the promoter region of inflammatory genes. CONCLUSION: NIK-SIX axis down-regulated inflammatory gene expression and plays a pivotal role in the maintenance of intestinal immune homeostasis.

Proton Magnetic Resonance Spectroscopy for Diagnosis of Non-Motor Symptoms in Parkinson's Disease.

Background: The current diagnosis of Parkinson's disease (PD) is mainly based on the typical clinical manifestations. However, 60% dopaminergic neurons have died when the typical clinical manifestations occur. Predictive neurobiomarkers may help identify those PD patients having non-motor disorders or in different stage and achieving the aim of early diagnosis. Up to date, few if any neuroimaging techniques have been described useful for non-movement disorders diagnosis in PD patients. Here, we investigated the alteration of metabolites in PD patients in different stage of PD and non-motor symptoms including sleep, gastrointestinal and cognitive dysfunction, by using the 1H-MRS. Methods: A total of 48 subjects were included between 2017 and 2019: 37 PD (15 men, age 47-82 years) and 11 healthy people (8 men, age 49-74 years). All participants underwent MRI and multi-voxel 1H-MRS examination within 3 days in admission. Six kinds of metabolites, such as creatine (Cr), N-acetyl aspartate/creatine (NAA/Cr), N-acetyl aspartate/choline (NAA/Cho), choline/creatine (Cho/Cr), lipid/creatine (LL/Cr), and myo-Inositol/creatine ratio (mI/Cr) were tested among the PD group and the control groups. Statistical analyses and correlation analyses were performed by using SPSS. The p < 0.05 was considered statistically significant. Results: Compared late PD group with a control group or early group, higher Cr ratio and lower NAA/Cr ratio were observed in the late PD group (p < 0.05). The mI/Cr in the late PD group was also lower than that in the early PD group (p < 0.05). Regarding the relationship between metabolites and NMS, Cho/Cr was higher in the sleep disorder group, whereas mI/Cr was lower in the gastrointestinal dysfunction group in comparison with the non-symptom groups. Moreover, Cr, Cho/Cr, mI/Cr, and LL/Cr were identified to have higher concentrations in the cognitive group in thalamus. Conclusions: Proton magnetic resonance spectroscopy is an advanced tool to quantify the metabolic changes in PD. Three biomarkers (Cr, NAA/Cr, and mI/Cr) were detected in the late stage of PD, suggesting that these markers might be potential to imply the progression of PD. In addition, subgroups analysis showed that MRS of thalamus is a sensitive region for the detection of cognitive decline in PD, and the alteration of neurochemicals (involving Cr, Cho, mI, and LL) may be promising biomarkers to predict cognitive decline in PD.

Construction of Two-Dimensional Fluorescent Covalent Organic Framework Nanosheets for the Detection and Removal of Nitrophenols.

In this work, we synthesized a two-dimensional fluorescent covalent-organic framework (TFPB-TTA COF) nanosheet by selecting and designing reactive monomers to realize the dual-functional processing of nitrophenols. The staggered benzene ring, triazine structure, and imine bond (C═N) of the TFPB-TTA COF can capture free nitrophenols through hydrogen bonding and conjugation interaction, and then, the photoinduced electron transfer and fluorescence resonance energy transfer (FRET) between the TFPB-TTA COF and nitrophenols affects the fluorescence emission of the TFPB-TTA COF, realizing the fluorescence sensing of nitrophenols. The large Ksv values and the low detection limit suggest that the TFPB-TTA COF can serve as sensitive and selective fluorescence sensors for nitrophenol detection in an aqueous system. At the same time, the strong interaction combined with the porous network structure of the TFPB-TTA COF facilitates the efficient adsorption and removal of nitrophenols. Especially for 2,4,6-trinitrophenol, the maximum adsorption capacity can reach 1045.53 mg/g with good recyclability and high structural stability of the TFPB-TTA COF. This work proposed a simple synthetic method for the construction of a fluorescent COF platform for the sensitive determination and efficient adsorption of nitrophenols.

Facile synthesis of fluorescent tungsten oxide quantum dots for telomerase detection based on the inner filter effect.

The traditional detection of telomerase activity is mainly based on the polymerase chain reaction (PCR), which has the disadvantages of being time-consuming and susceptible to interferences; thus, here, we propose a facile method for the fabrication of fluorescent tungsten oxide quantum dots (WOx QDs) and employ them for telomerase activity sensing. It is found that the fluorescence of WOx QDs can be significantly quenched by hemin based on the inner filter effect (IFE). However, in the presence of telomerase, the primer-DNA can be extended to generate repeating units of TTAGGG to form G-quadruplex and thus, hemin can be encapsulated to reduce its absorbance, resulting in decreased IFE and efficient fluorescence recovery of WOx QDs. Based on the fluorescence changes of IFE between hemin and WOx QDs, the telomerase activity within the range of 50-30 000 HeLa cells can be detected and the lowest detection amount can reach 17 cells. The method exhibits good versatility that can also be applied to telomerase detection in A549 and L929 cells. In addition, because of the good biocompatibility of the sensor, it can be used for the real-time monitoring of telomerase activity in living cells, thus showing great potential in tumor diagnosis and inhibitor drug screening.

Regulation of multiple energy transfer processes in a simple nano-system for sensitive telomerase detection.

Telomerase, as a potential biomarker for early cancer diagnostics and therapies, has attracted considerable interests concerning its detection and monitoring. Herein, we develop a novel method for sensitive detection of telomerase activity by designing a gold nanoparticles/graphene oxide (AuNPs/GO) probe. The AuNPs were functionalized with a telomerase substrate (TS) primer and a 6-carboxy-fluorescein (FAM)-modified complementary DNA (P1). In the absence of telomerase, P1 exists in the random-coiled conformation, and the fluorescence resonance energy transfer (FRET) from FAM to AuNPs and GO results in efficient fluorescence quenching. In the presence of telomerase, the multiple hybridization between TS extension products and P1 leads to the conformation transition of P1 from single-stranded DNA to double-stranded rigid structure, and thus the FRET process can be prevented with the efficient fluorescence recovery. The metal enhanced fluorescence (MEF) effect between FAM and AuNPs can further effectively enhance the fluorescence of FAM, and thus the sensitivity and specificity of telomerase detection can be remarkably improved. It is worth mentioning that the proposed strategy does not need to design complex hairpin structure and allows the measurement of telomerase activity in three crude cell extracts equivalent to 7 HeLa cells, 8 A549 cells and 8 L929 cells in 1 h. In addition, the present sensing platform can be applied to inhibitor screening, in situ telomerase imaging, and intracellular drug delivery.

Cobalt phosphide nanowires for fluorometric detection and in-situ imaging of telomerase activity via hybridization chain reactions.

The authors describe cobalt phosphide (CoP) nanowires for use in sensitive fluorometric determination of the activity of the enzyme telomerase. A hybridization chain reaction (HCR) is applied to amplify the signal and carboxyfluorescein (FAM)-labelled hairpin probes (H1 and H2) are applied to match the telomeric DNA sequence. The CoP nanowires act as both the photoinduced electron transfer (PET) acceptor to induce fluorescence quenching, and also as an efficient probe carrier to facilitate telomerase imaging in living cells. The telomerase-triggered primer extension initiates an alternating hybridization reaction between H1 and H2. These result in the dissociation of FAM-labelled probes from CoP nanowires and thus an enhancement of the green fluorescence. The method is fairly simple and was applied to the detection of three types of cancer cells. The detection limit is as low as 7 cells (in case of HeLa cells). Conceivably, the method has a large potential in terms of inhibitor drug screening. Graphical abstract Schematic presentation of telomerase detection based on cobalt phosphide (CoP) nanowires and hybridization chain reaction (HCR). The telomerase-triggered primer extension can initiate the alternating hybridization reaction between carboxyfluorescein (FAM)-labelled hairpin probes (H1 and H2), and the generated long DNA duplex cannot be adsorbed on the CoP nanowires. This prevents the photoinduced electron transfer (PET) from FAM to CoP nanowires.

A facile graphene oxide-based fluorescent nanosensor for the in situ "turn-on" detection of telomerase activity.

A facile and sensitive method for the quantitative detection of telomerase and in situ imaging of intracellular telomerase is developed by using a graphene oxide (GO)-based fluorescent nanosensor. The nanosensor consists of a fluorescent DNA (P1) adsorbed on the GO surface. Here, GO serves not only as a fluorescence quencher but also as a carrier to successfully transport P1 into cancer cells as a signal reporter. P1 is a dye-labeled single-stranded DNA complementary to the telomeric repeated sequence, and initially the combination of P1 and GO exhibits minimal background fluorescence. When telomerase extends its repeat units of TTAGGG on the 3'-end of the primer-DNA, the fluorescence of P1 is subsequently recovered because the telomeric repeated sequence can hybridize with P1 and liberate it from the GO surface. This method enables the determination of telomerase activity down to 10 cells. For the in situ detection of telomerase, upon endocytosis of the P1/GO combinatorial probe into living cancer cells, the intracellular telomerase extends its primer to produce the telomeric repeated sequence and then turns on the fluorescence of P1, which can be directly monitored by confocal laser scanning microscopy. The feasibility of the assay is further investigated by treating with telomerase-related drugs, and the results demonstrate its potential in antitumor drug screening and cancer therapy evaluation.

Combination of LC/MS and GC/MS based metabolomics to study the hepatotoxic effect of realgar nanoparticles in rats.

Realgar nanoparticles (NPs) are increasingly used as therapeutic agents for their enhanced anti-proliferation effect and cytotoxicity on cancer cells. However, the alteration of particle size may enhance biological reactivity as well as toxicity. A LC/MS and GC/MS based metabolomics approach was employed to explore the mechanism of realgar NPs-induced hepatotoxicity and identify potential biomarkers. Male Sprague-Dawley rats were administrated intragastrically with realgar or realgar NPs at a dose of 1.0 g·kg-1·d-1 for 28 days and toxic effects of realgar NPs on liver tissues were examined by biochemical indicator analysis and histopathologic examination. Increased levels of serum enzymes and high hepatic steatosis were discovered in the realgar NPs treated group. Multivariate data analysis revealed that rats with realgar NPs-induced hepatotoxicity could be distinctively differentiated from the animals in the control and realgar treated groups. In addition, 21 and 32 endogenous metabolites were apparently changed in the serum and live extracts, respectively. Realgar NPs might induce free fatty acid and triglyceride accumulation, resulting in hepatotoxicity. In conclusion, the present study represents the first comprehensive LC/MS- and GC/MS-based metabolomics analysis of realgar NPs-induced hepatotoxicity, which may help further research of nanotoxicity.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury.

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl4-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl4-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl4-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

Quantitative Evaluation of the Compatibility Effects of Huangqin Decoction on the Treatment of Irinotecan-Induced Gastrointestinal Toxicity Using Untargeted Metabolomics.

Huangqin decoction (HQD), a traditional Chinese medicine (TCM), has been widely used to treat gastrointestinal syndrome in China for thousands of years. Chemotherapy drug irinotecan (CPT-11) is used clinically to treat various kinds of cancers but limited by its side effects, especially delayed diarrhea. Nowadays, HQD has been proved to be effective in attenuating the intestinal toxicity induced by CPT-11. HQD consists of four medicinal herbs including Scutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. Due to its complexity, the role of each herb and the multi-herb synergistic effects of the formula are poorly understood. In order to quantitatively assess the compatibility effects of HQD, mass spectrometry-based untargeted metabolomics studies were performed. The serum metabolic profiles of rats administered with HQD, single S. baicalensis decoction, S. baicalensis-free decoction and baicalin/baicalein combination were compared. A time-dependent trajectory upon principal component analysis was firstly used to visualize the overall differences. Then metabolites deregulation score and relative area under the curve were calculated and used as parameters to quantitatively evaluate the compatibility effects of HQD from the aspect of global metabolic profile and the specifically altered metabolites, respectively. The collective results indicated that S. baicalensis played a crucial role in the therapeutic effect of HQD on irinotecan-induced diarrhea. Both HQD and SS decoction regulated glycine, serine and threonine pathway. This study demonstrated that metabolomics was a promising tool to elucidate the compatibility effects of TCM or combinatorial drugs.

Renal Medulla is More Sensitive to Cisplatin than Cortex Revealed by Untargeted Mass Spectrometry-Based Metabolomics in Rats.

Nephrotoxicity has long been the most severe and life-threatening side-effect of cisplatin, whose anticancer effect is therefore restricted. Previous pathological studies have shown that both renal cortex and medulla could be injured by cisplatin. Our TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) assay results further uncovered that medulla subjected more severe injury than cortex. In order to depict the underlying metabolic mechanism of spatial difference in response to cisplatin, in the present study, mass spectrometry-based untargeted metabolomics approach was applied to profile renal cortex and medulla metabolites of rat after receiving a single dose of cisplatin (2.5, 5 or 10 mg/kg). Eventually, 53 and 55 differential metabolites in cortex and medulla were screened out, respectively. Random forest, orthogonal partial least squares-discriminant analysis and metabolic cumulative fold change analysis revealed that metabolic changes in medulla were more obviously dose-dependent than those in cortex, which confirmed the conclusion that medulla was more sensitive to cisplatin exposure. Furthermore, 29 intermediates were recognized as the most contributive metabolites for the sensitivity difference. Metabolic pathways interrupted by cisplatin mainly included amino acid, energy, lipid, pyrimidine, purine, and creatine metabolism. Our findings provide new insight into the mechanism study of cisplatin-induced nephrotoxicity.

Highly selective and sensitive surface enhanced Raman scattering nanosensors for detection of hydrogen peroxide in living cells.

Determination of hydrogen peroxide (H2O2) with high sensitivity and selectivity in living cells is a challenge for evaluating the diverse roles of H2O2 in the physiological and pathological processes. In this work, we present novel surface enhanced Raman scattering (SERS) nanosensors, 4-carboxyphenylboronic acid (4-CA) modified gold nanoparticles (Au NPs/4-CA), for sensing H2O2 in living cells. The nanosensors are based on that the H2O2-triggered oxidation reaction with the arylboronate on Au NPs would liberate the phenol, thus causing changes of the SERS spectra of the nanosensors. The results show the nanosensors feature higher selectivity for H2O2 over other reactive oxygen species, abundant competing cellular thiols and biologically relevant species, as well as excellent sensitivity with a low detection limit of 80 nM, which fulfills the requirements for detection of H2O2 in a biological system. In addition, the SERS nanosensors exhibit long term stability against time and pH, and high biocompatibility. More importantly, the presented nanosensors can be successfully used for monitoring changes of H2O2 levels within living biological samples upon oxidative stress, which opens up new opportunities to study its cellular biochemistry.

[Experimental research of oil vapor pollution control for gas station with membrane separation technology].

Two kinds of membranes modules, vapor retained glassy membrane based on PEEK hollow fiber membrane modules and vapor permeated rubbery membrane system based on GMT plate-and-frame membrane modules, were used to control the oil vapor pollution during the course of receiving and transferring gasoline in oil station. The efficiencies of the membrane module and the membrane system of them were evaluated and compared respectively in the facilities which were developed by ourselves. It was found that both the two kinds of membranes modules had high efficiency for the separation of VOCs-air mixed gases, and the outlet vapor after treatment all can meet the national standard. When the vapor-enriched gas was returned to the oil tank to simulate the continuously cycle test, the concentration of VOCs in the outlet was also below 25 g x m(-3).

[CFD numerical simulation onto the gas-liquid two-phase flow behavior during vehicle refueling process].

With the gradual improvement of environmental regulations, more and more attentions are attracted to the vapor emissions during the process of vehicle refueling. Research onto the vehicle refueling process by means of numerical simulation has been executed abroad since 1990s, while as it has never been involved so far domestically. Through reasonable simplification about the physical system of "Nozzle + filler pipe + gasoline storage tank + vent pipe" for vehicle refueling, and by means of volume of fluid (VOF) model for gas-liquid two-phase flow and Re-Normalization Group kappa-epsilon turbulence flow model provided in commercial computational fluid dynamics (CFD) software Fluent, this paper determined the proper mesh discretization scheme and applied the proper boundary conditions based on the Gambit software, then established the reasonable numerical simulation model for the gas-liquid two-phase flow during the refueling process. Through discussing the influence of refueling velocity on the static pressure of vent space in gasoline tank, the back-flowing phenomenon has been revealed in this paper. It has been demonstrated that, the more the flow rate and the refueling velocity of refueling nozzle is, the higher the gross static pressure in the vent space of gasoline tank. In the meanwhile, the variation of static pressure in the vent space of gasoline tank can be categorized into three obvious stages. When the refueling flow rate becomes higher, the back-flowing phenomenon of liquid gasoline can sometimes be induced in the head section of filler pipe, thus making the gasoline nozzle pre-shut-off. Totally speaking, the theoretical work accomplished in this paper laid some solid foundation for self-researching and self-developing the technology and apparatus for the vehicle refueling and refueling emissions control domestically.