Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. RESULTS: Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. CONCLUSIONS: The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.

Phosphorylation of RasGRP1 by Shc3 prevents RasGRP1 degradation and contributes to Ras/c-Jun activation in hepatocellular carcinoma.

Ras guanine nucleotide-releasing protein 1 (RasGRP1), a Ras activator, is upregulated in hepatocellular carcinoma (HCC) and other kinds of cancer and is associated with the poor prognosis of patients. However, little is known about the underlying regulatory mechanisms of RasGRP1 in the context of cancer. Here, we report that RasGRP1 physically interacted with the adaptor protein Src homolog and collagen homolog 3 (Shc3). Moreover, RasGRP1 C-terminus domain (aa 607-797) bound to the central collagen-homology 1 (CH1) domain of Shc3. Subsequently, Shc3 enhanced the RasGRP1 tyrosine phosphorylation rate and stability by inhibiting its ubiquitination. Notably, the phosphorylation-mimicking mutants of RasGRP1, RasGRP1 Y704A, and Y748A, rescued the phosphorylation and ubiquitination levels of RasGRP1 in HCC cells. Further investigation showed that the RasGRP1 and Shc3 interaction induced activation of Ras and c-Jun, resulting in cell proliferation in vitro. Moreover, the regulation of Shc3/RasGRP1/Ras/c-Jun signal transduction was confirmed in vivo using the subcutaneous xenograft mouse model. Thus, we propose that continuous Shc3 overexpression may be a possible mechanism for maintaining RasGRP1 stability and that persistent activation of Ras/c-Jun signaling through the interaction of RasGRP1 and Shc3 is a key event increasing cell proliferation. Our findings suggest that the interaction of RasGRP1 and Shc3 plays an important role in HCC tumorigenesis and suggests the potential clinical usage of novel biomarkers and therapeutic targets in HCC.

Spin Hall effect of transmitted light through α-Li3N-type topological semimetals.

The spin Hall effect of light occurring in topological semimetals provides unprecedented opportunities to exploit novel photonic properties and applications. In particular, pristine α-Li3N-type crystal has recently been predicted to be a type-I nodal-line semimetal based on density functional theory. Herein, the spin Hall effect of transmitted light through thin films of α-Li3N-type topological semimetals is investigated. We show that the prominent intense peak and dip emerging in the spectra of spin Hall shifts occur at the high-energy side of interband absorption of α-Li3N-type semimetals and show redshifts with increasing the incident angle or permittivity of the exit medium. In addition, type-I nodal-line semimetal under a compressive lattice strain is transformed into a type-II one such that the main intense peak and dip show blueshifts. Inversely, the tensile strain induces the formation of a triply degenerate nodal point in α-Li3N-type semimetals, causing the main intense peak and dip to show redshifts. Moreover, the influences of alloying and hole-doping in α-Li3N-type semimetals on the spin Hall effect of light are also discussed. Our findings may provide clear strategies to accurately engineer and detect the structural or phase change in topological materials.

Site-bond percolation model of epidemic spreading with vaccination in complex networks.

To study disease transmission with vaccination based on the network, we map an SIR model to a site-bond percolation model. In the case where the vaccination probability is zero, this model degenerates into a bond percolation model without the immunization. Using the method of generation functions, we obtain exact theoretical results for the epidemic threshold and the average outbreak size. From these exact solutions, we find that the epidemic threshold increases while the average outbreak size decreases with vaccination probability. Numerical simulations show that the size of giant component S increases with transmissibility T but decreases with the probability of vaccination. In addition, we compare the epidemic threshold and the size of the giant component for a Poisson network, an exponential network and a power-law network using numerical simulations. When the probability of vaccination is fixed, the epidemic threshold is the smallest for heterogeneous networks and the size of giant component S in homogeneous networks becomes largest for large transmissibility T(T close to 1).

Correlational research on facial and clinical characteristics of adolescents with obsessive-compulsive disorder.

BACKGROUND: The neurodevelopmental model of obsessive-compulsive disorder (OCD) suggests that the neurodevelopmental changes in the ventral striatal circuit of the prefrontal lobe are associated with the initial symptoms of OCD. Facial morphology is one of the most consistent anatomical phenotypes of neurodevelopmental disorders, which can reflect brain structure and function. Facial deformity, an easily measured index of brain malformation, can reflect abnormal brain structure and function. Therefore, this study aims to explore the relationship between clinical features and neurodevelopment of adolescents with OCD through facial morphology. METHODS: The enrolled study sample comprised 40 adolescents diagnosed with OCD using the Obsessive Compulsive Inventory-Child Version (OCI-CV) and 38 healthy controls (HCs). Facial photos, 21 facial diameters, and 9 facial angles were collected using image software. RESULTS: In males, lower lip red height was significantly lower in OCD patients than in HCs (P < 0.025); no significant differences were observed in other facial indicators (all P > 0.025). In females, the nasolabial angle was smaller in OCD patients than in HCs (P < 0.025); no significant differences were observed in other facial indicators (all P > 0.025). The difference in lower lip red height between the OCD group and HC group was positively correlated with neutralizing symptoms (r = 0.401, P < 0.05). CONCLUSIONS: Male OCD patients had a thinner lower lip and female OCD patients had smaller nasolabial angles. The facial features of adolescents with OCD were positively correlated with lower lip redness and neutralizing symptoms.

Effects of exogenous ascorbic acid on the mycelia growth and primordia formation of Pleurotus ostreatus.

Primordia formation is the first and most critical step in the development of fruiting bodies of edible fungi. In this study, the effects of exogenous ascorbic acid (ASA) on the Pleurotus ostreatus mycelia growth and primordia formation were researched and the results showed that the growth rate of P. ostreatus mycelia was accelerated and the time of primordia formation was advanced. The protein content and ascorbate oxidase (AAO) activity analysis showed that with the increase of ASA concentration, the protein content of mycelia first decreased and then increased, and in a certain concentration range, exogenous ASA could significantly promote the activity of AAO. Further expression analysis of the development regulating genes (Pofst3 and Pofst4) as well as blue light receptor coding genes (PoWC-1 and PoWC-2) showed the expression levels of those four genes all changed after the exogenous ASA addition, which indicated that the expression changes of PoWC-1 and PoWC-2, two key genes in the light morphogenesis, might affect the expression levels of development regulating genes Pofst3 and Pofst4, so as to lead to the formation of primordia in advance.

How to relieve stress in adult child caregivers of the older adults with disabilities: a survey study from the city of Nanjing, China.

The care of older adults with disabilities (OADs) in China is mostly provided by their adult offspring. As the population continues to age, carer stress will increase. A survey of 900 adult child caregivers of OADs was conducted in Nanjing City, Jiangsu Province, China, and used to investigate the status and stress levels of caregivers in order to explore effective support for offspring caregivers and suggest improvements to the social care system. Multiple linear regression models were used to examine the effects of coping strategies on carer stress. Caregivers experienced stress at moderate or high levels due to physical, psychological, financial, and work issues. Stress was significantly associated with OADs' health status and self-care ability, and the amount of care time. Caregivers sought help from their families to care for elderly parents, which significantly relieved stress. The purchase of social care services and professional medical services for OADs significantly reduced stress; however, for elderly persons with high self-care ability, the purchase of social care services increased caregiver stress, while government-subsidized family nursing allowances reduced it. It is necessary to focus on the role of family care to stimulate mutual family support, and to integrate society and government support systems.

Prevalence and antimicrobial resistance of Mycoplasmas and Chlamydiae in patients with genital tract infections in Shanghai, China.

The infections of Mycoplasmas and Chlamydiae are still severe in patients with genital tract diseases and antimicrobial resistance for these organisms has been changing in recent years. In this study, we reported the prevalence status of Ureaplasma urealyticum, Mycoplasma hominis and Chlamydia trachomatis in 965 patients with genital tract infection in Shanghai from January 2011 to December 2014 and analyzed the antimicrobial resistance of U. urealyticum and M. hominis to 12 kinds of antimicrobial drugs by using commercial kits and SPSS13.0 software. Here, we found the infection of U. urealyticum was the most frequent among these three organisms. The total infection rate for containing any organisms of them was 49.5%, and it has been increasing in recent 4 years. Positive rate in female (53.3%) was higher than male's (34.8%), and the high risk population was 20-39 years old (56.7%). Besides, U. urealyticum and M. hominis displayed relative lower resistance rates to minocycline, doxycycline, josamycin and gatifloxacin (6.5%, 7.2%, 13.5% and 8.6%, respectively). However, for erythromycin, roxithromycin, thiamphenicol and clindamycin, the resistance rates were relatively high (41.9%, 47.2%, 62.3% and 74.9%, respectively). U. urealyticum and M. hominis displayed a declined trend of the antimicrobial resistance to 12 kinds of drugs detected in this study. In total, these preliminary data showed the prevalence of Mycoplasmas and Chlamydiae in patients and the antimicrobial resistance status of Mycoplasmas, which has use for reference on both prevention and treatment of diseases caused by them.

Stat3 inhibits Beclin 1 expression through recruitment of HDAC3 in nonsmall cell lung cancer cells.

Recent studies have shown that Beclin 1, a key regulator of autophagic process, is frequently downregulated and may serve as an independent prognostic biomarker for nonsmall cell lung cancer. However, the molecular mechanisms underlying its downregulation remain poorly understood. The signal transducer and activator of transcription 3 (Stat3) is a transcription factor which plays a crucial role for multiple tumor growth and progression. Here, we demonstrate that Beclin 1 is a direct transcriptional target of Stat3 in lung cancer cells. Interleukin-6 (IL-6) treatment or transfection of a constitutively activated Stat3 in AGS and NCI-H1650 cells inhibited Beclin 1 expression. At the molecular level, we further revealed that Stat3 could directly bind to the promoter region of Beclin 1 and repressed its transcription through recruiting histone deacetylase 3 (HDAC3). Collectively, our results suggest that the activated Stat3 may represent an important mechanism for Beclin 1 downregulation in nonsmall cell lung cancer development.

[Phantom holder of CT couch].

This article describes a phantom holder in CT couch which adjusted easily and accurately, installed easily. The holder mainly include removing and locking equipment between phantom holder and table top, move horizontally equipment between left and right, rotating equipment between left and right. After holder and table top fixed one part, holder with phantom can move horizontally, front and back, rotate between left and right in a small angle, in order to make operator test phantoms accurately and easily. At the same time, this phantom holder realized free adjustment after first adjustments, which shortened operator work time.

[Method and application for improving the load capacity of CT diagnosis table top].

In the load capacity test of CT diagnosis table top, by analyzing the easy destroy area and related test data for the table top, using a simple mechanical auxiliary support structure in local area of the table top to solve the insufficient loading strength problem of table top and obtain significant results during the actual product usage.

The impact of social exclusion on impulsive buying behaviour of consumers on online platforms: Samples from China.

Social exclusion is a common phenomenon in modern social life that has significant negative effects on those who were excluded. The excluded may adopt strategic impulsive consumption behaviors in order to gain a sense of belonging and repair social relations, and the rapid development of online shopping platforms has intensified the occurrence of impulsive purchasing behaviors. Therefore, the internal mechanism between the two needs to be clarified. This study utilised SPSS 26.0, Mplus8.0 and HLM6.08 to analyse the data from 417 questionnaires, focused on exploring the internal mechanism between social exclusion and impulsive buying behaviour, and yielded the following conclusions. (1) Social exclusion is positively correlated with impulsive purchasing behaviour. (2) Relative deprivation plays a mediating role between social exclusion and impulsive buying behaviour. (3) The need to belong plays an intermediary role between social exclusion and impulsive buying behaviour. (4) Self-control plays a moderating role between social exclusion and impulsive buying behaviour. These conclusions could provide a basis for enterprises to formulate rational marketing strategies and create consumer demand.

Emerging insights into the roles of ANGPTL8 beyond glucose and lipid metabolism.

Angiopoietin-like protein 8 (ANGPTL8) is a secreted protein predominantly expressed in liver and adipose tissue. ANGPTL8 modulates the clearance of triglycerides (TGs) by suppressing the activity of lipoprotein lipase (LPL) within the plasma. Previous studies found that circulating ANGPTL8 levels were significantly increased in metabolic disorder-related diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Whether ANGPTL8 has a direct pathogenic role in these diseases remains to be determined. In this review, we summarize the emerging roles of ANGPTL8 in the regulation of inflammation, tumours, circulatory system-related diseases, and ectopic lipid deposition, which may provide new insights into the diverse functions of ANGPTL8 in various diseases beyond its well-established functions in glucose and lipid metabolism.

High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.

Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of Lactobacillus, Bifidobacterium and Akkermansias revealed that the proportions of beneficial gut microbes were enriched by the high-fiber diet, while the abundances of Desulfovibrio, Klebsiella and other opportunistic pathogens were decreased. Therefore, the current study demonstrated that the intestinal microbiota alterations which were influenced by the high-fiber diet could improve the serum metabolism and emotional mood of patients with T2DM.

Analysis of a two-patch SIS model with saturating contact rate and one- directing population dispersal.

In this paper, a two-patch SIS model with saturating contact rate and one-directing population dispersal is proposed. In the model, individuals can only migrate from patch 1 to patch 2. The basic reproduction number $ R_0^1 $ of patch 1 and the basic reproduction number $ R_0^2 $ of patch 2 is identified. The global dynamics are completely determined by the two reproduction numbers. It is shown that if $ R_0^1 < 1 $ and $ R_0^2 < 1 $, the disease-free equilibrium is globally asymptotically stable; if $ R_0^1 < 1 $ and $ R_0^2 > 1 $, there is a boundary equilibrium which is globally asymptotically stable; if $ R_0^1 > 1 $, there is a unique endemic equilibrium which is globally asymptotically stable. Finally, numerical simulations are performed to validate the theoretical results and reveal the influence of saturating contact rate and migration rate on basic reproduction number and the transmission scale.

Oxidation-reduction potential affects medium-chain fatty acid ethyl ester production during wine alcohol fermentation.

The medium-chain fatty acid ethyl esters (MCFAEEs) are a group of important aroma compounds generated during wine production. Wine alcohol fermentation involves several redox processes, which are affected by the oxidation-reduction potential (ORP). However, the mechanism via which ORP regulates MCFAEE production remains unclear. To investigate the effect of ORP on MCFAEE production, wine alcohol fermentation was performed using Saccharomyces cerevisiae under different ORPs. The results demonstrated that the ORPs studied (except for 90 mV) did not significantly affect cell growth, sugar consumption, and ethanol production, while the MCFAEE concentration in the simulated wines can be manipulated by ORP operation. MCFAEE levels increased till 96 h, and then decreased. The maximum MCFAEE level of 1222.97 µg/L was obtained after 96 h at 0 mV, which was 45.32% higher than that of the control. During the increase, higher relative expression of ACC1, FAS1, FAA2 and EEB1, elevated external citric acid flux, and moderate intracellular NADP+/NADPH ratio were observed at 0 mV compared to that at other ORPs. During the decrease, lowest relative expression of POX1 was detected at 0 mV. We showed for the first time the relationship between ORP operation and MCFAEE production in winemaking, which will improve the aroma quality of wine.

Pretreatment with the active fraction of Rhodiola tangutica (Maxim.) S.H. Fu rescues hypoxia-induced potassium channel inhibition in rat pulmonary artery smooth muscle cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the active fraction of Rhodiola tangutica (Maxim.) S.H. Fu (ACRT) dilates pulmonary arteries and thwarts pulmonary artery remodelling. The dilatation effect of ACRT on pulmonary artery vascular rings could be reduced by potassium (K+) channel blockers. However the exact mechanisms of ACRT on ion channels are still unclear. AIM OF THE STUDY: This study aimed to investigate whether the effect of ACRT on K+ channels inhibits cell proliferation after pulmonary artery smooth muscle cells (PASMCs) are exposed to hypoxia. MATERIALS AND METHODS: The whole-cell patch-clamp method was used to clarify the effect of ACRT on the K+ current (IK) of rat PASMCs exposed to hypoxia. The mRNA and protein expression levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The intracellular calcium (Ca2+) concentration ([Ca2+]i) values in rat PASMCs were detected by laser scanning confocal microscopy. The cell cycle and cell proliferation were assessed using flow cytometry analysis and CCK-8 and EdU assays. RESULTS: ACRT pretreatment alleviated the inhibition of IK induced by hypoxia in rat PASMCs. Compared with hypoxia, ACRT upregulated voltage-dependent K+ channel (Kv) 1.5 and big-conductance calcium-activated K+ channel (BKCa) mRNA and protein expression and downregulated voltage-dependent Ca2+ channel (Cav) 1.2 mRNA and protein expression. ACRT decreased [Ca2+]i, inhibited the promotion of cyclin D1 and proliferating cell nuclear antigen (PCNA) expression, and prevented the proliferation of rat PASMCs exposed to hypoxia. CONCLUSION: In conclusion, the present study demonstrated that ACRT plays a key role in restoring ion channel function and then inhibiting the proliferation of PASMCs under hypoxia, ACRT has preventive and therapeutic potential in hypoxic pulmonary hypertension.

Partially light-controlled imaging system based on High Temperature Poly-Silicon Thin Film Transistor-Liquid Crystal Display.

A partially light-controlled imaging system is proposed as a novel device. It is used to improve the imaging quality at the illumination of 1.979 x 10(5)lx by means of mitigating image contrast. It consists of a High Temperature Poly-Silicon Thin Film Transistor-Liquid Crystal Display (HTPS TFT-LCD), which is set between the lens and CCD and is coupled with CCD by the optical fiber taper. The transmittance of pixelated LCD can be controlled by Field-Programmable Gate Array to realize the partially light-controlled and thus dynamic range of the imaging system can be extended. Samples of indoor objects and outdoor license plate are photographed by the prototype imaging system under strong light. The imaging results of this novel system are satisfactory with better restored details, compared with the photos taken by normal CCD camera (WAT-231S2) which uses aperture and shutter to control the overall light intensity.

Multifunctional composite nanoparticles based on hyaluronic acid-paclitaxel conjugates for enhanced cancer therapy.

The efficient delivery of chemotherapeutic drugs to the tumor tissues unavoidably encounters numerous obstacles, such as poor tumor targeting capability, slow intracellular drug release and massive accumulation in the liver. In this study, by self-assembling methoxy poly (ethylene glycol)-poly (lactide) block copolymer (mPEG-PLA) and hyaluronic acid-paclitaxel conjugate (HA-PTX), the composite nanoparticles (mPPHP NPs) were fabricated for efficient therapy of cancer. mPPHP NPs formed self-assembled nanoparticles (116 nm in diameter) with a narrow size distribution; and showed a rapid release of PTX in the presence of hyaluronidase and esterase. mPPHP NPs exhibited enhanced internalization by cells via CD44 receptors and selected cytotoxicity against A549 cells in vitro. More importantly, compared with other PTX formulations, mPPHP NPs were demonstrated to present the reduced liver accumulation, excellent tumor-targeting ability and superior antitumor efficacy in vivo, with a TIR of 75.9%. The multifunctional composite nanoparticles could be developed as a promising nano-carrier for improved therapeutic efficacy.

A novel assessment system of toxicity and stability of CuO nanoparticles via copper super sensitive Saccharomyces cerevisiae mutants.

CuO nanoparticles (CuO-NPs) toxicity in organisms is contributed mainly through the copper uptake by both the ionic and nanoparticle form. However, the relative uptake ratio and bioavailability of the two different forms is not well known due to a lack of sensitive and effective assessment systems. We developed a series of both copper resistant and hyper sensitive Saccharomyces cerevisiae mutants to investigate and compare the effects of CuO-NPs and dissolved copper (CuCl2), on the eukaryote with the purpose of quantitating the relative contributions of nanoparticles and dissolved species for Cu uptake. We observed the toxicity of 10 mM CuO-NPs for copper sensitive strains is equal to that of 0.5 mM CuCl2 and the main toxic effect is most likely generated from oxidative stress through reactive oxygen species (ROS) production. About 95% CuO-NPs exist in nanoparticle form under neutral environmental conditions. Assessing the cellular metal content of wild type and copper transporter 1(CTR1) knock out cells showed that endocytosis is the major absorption style for CuO-NPs. This study also found a similar toxicity of Ag for both 10 mM Ag-NPs and 0.2 mM AgNO3 in the copper super sensitive strains. Our study revealed the absorption mechanism of soluble metal based nanomaterials CuO-NPs and Ag-NPs as well as provided a sensitive and delicate system to precisely evaluate the toxicity and stability of nanoparticles.