Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice.

In diabetes, pancreatic ß-cells gradually lose their ability to secrete insulin with disease progression. ß-cell dysfunction is a contributing factor to diabetes severity. Recently, islet cell heterogeneity, exemplified by ß-cell dedifferentiation and identified in diabetic animals, has attracted attention as an underlying molecular mechanism of ß-cell dysfunction. Previously, we reported ß-cell dedifferentiation suppression by calorie restriction, not by reducing hyperglycemia using hypoglycemic agents (including sodium-glucose cotransporter inhibitors), in an obese diabetic mice model (db/db). Here, to explore further mechanisms of the effects of food intake on ß-cell function, db/db mice were fed either a high-carbohydrate/low-fat diet (db-HC) or a low-carbohydrate/high-fat diet (db-HF) using similar calorie restriction regimens. After one month of intervention, body weight reduced, and glucose intolerance improved to a similar extent in the db-HC and db-HF groups. However, ß-cell dedifferentiation did not improve in the db-HC group, and ß-cell mass compensatory increase occurred in this group. More prominent fat accumulation occurred in the db-HC group livers. The expression levels of genes related to lipid metabolism, mainly regulated by peroxisome proliferator-activated receptor α and γ, differed significantly between groups. In conclusion, the fat/carbohydrate ratio in food during calorie restriction in obese mice affected both liver lipid metabolism and ß-cell dedifferentiation.

In vitro study on antioxidant and lipid-lowering activities of tobacco polysaccharides.

Tobacco polysaccharides were extracted by hot water extraction, and purified and separated using DEAE-52 cellulose chromatography columns, and three purified polysaccharide fractions, YCT-1, YCT-2, and YCT-3, were finally obtained. The physicochemical properties of the three fractions were analyzed by ultraviolet spectroscopy, high-performance liquid chromatography and high-performance gel chromatography. The in vitro antioxidant activity of tobacco polysaccharides was compared among different fractions by using DPPH radical, hydroxyl radical scavenging assay and potassium ferricyanide method. The in vitro hypoglycemic activity was compared using α-amylase and α-glucosidase activity inhibition assay. And the in vitro hypolipidemic activity were investigated by using pancreatic lipase activity inhibition assay and HepG-2 intracellular lipid accumulation assay. All the results showed that the constituent monosaccharides of the three tobacco polysaccharide fractions were similar, but the molar percentages of each monosaccharide were different. The average molecular weights of the three components were 27,727 Da, 27,587 Da, and 66,517 Da, respectively, and the scavenging activities on DPPH radicals and hydroxyl radicals were at a high level with good quantitative-effect relationships. The reducing power were much lower than that of the positive control VC, and the three polysaccharide fractions had a weak inhibitory ability on α-amylase activity, but showed excellent inhibitory ability on α-glucosidase and pancreatic lipase activity. In addition, the results of cellular experiments showed that all three fractions were able to inhibit lipid over-accumulation in HepG-2 cells by increasing the mRNA expression levels of PPAR-α, CPT-1A, and CYP7A1 genes, and the tobacco polysaccharide YCT-3 showed the best effect. The mechanism by which YCT-3 ameliorated the over-accumulation of intracellular lipids in HepG-2 cells was found to be related to its influence on the expression of miR-155-3p and miR-17-3p in the exosomes of HepG-2 cells.

KINASE-INDUCIBLE DOMAIN INTERACTING 8 regulates helical pod morphology in Medicago truncatula.

Leguminosae exhibits a wide diversity of legume forms with varying degrees of spiral morphologies, serving as an ideal clade for studying the growth and development of spiral organs. While soybean (Glycine max) develops straight pods, the pod of the model legume Medicago truncatula is a helix structure. Despite the fascinating structures and intensive description of the pods in legumes, little is known regarding the genetic mechanism underlying the highly varied spirality of the legume pods. In this study, we found that KINASE-INDUCIBLE DOMAIN INTERACTING 8 (MtKIX8) plays a key role in regulating the pod structure and spirality in M. truncatula. Unlike the coiled and barrel-shaped helix pods of the wild type, the pods of the mtkix8 mutant are loose and deformed and lose the topologic structure as observed in the wild-type pods. In the pods of the mtkix8 mutant, the cells proliferate more actively and overly expand, particularly in the ventral suture, resulting in uncoordinated growth along the dorsal and ventral sutures of pods. The core cell cycle genes CYCLIN D3s are upregulated in the mtkix8 pods, leading to the prolonged growth of the ventral suture region of the pods. Our study revealed the key role of MtKIX8 in regulating seed pod development in M. truncatula and demonstrates a genetic regulatory model underlying the establishment of the helical pod in legumes.

New-onset hypertension as a contributing factor to the incidence of atrial fibrillation in the elderly.

Hypertension and atrial fibrillation are closely related. However, hypertension is already prevalent in young adults, but atrial fibrillation usually occurs in the elderly. In the present analysis, we investigated incident atrial fibrillation in relation to new-onset hypertension in an elderly Chinese population. Our study participants were elderly (≥65 years) hypertensive residents, recruited from community health centers in the urban Shanghai (n = 4161). Previous and new-onset hypertension were defined as the use of antihypertensive medication or elevated systolic/diastolic blood pressure (≥140/90 mmHg), respectively, at entry and during follow-up on ≥ 2 consecutive clinic visits. Atrial fibrillation was detected by a 30-s single-lead electrocardiography (ECG, AliveCor® Heart Monitor) and further evaluated with a regular 12-lead ECG. During a median of 2.1 years follow-up, the incidence rate of atrial fibrillation was 7.60 per 1000 person-years in all study participants; it was significantly higher in patients with new-onset hypertension (n = 368) than those with previous hypertension (n = 3793, 15.76 vs. 6.77 per 1000 person-years, P = 0.02). After adjustment for confounding factors, the hazard ratio for the incidence of atrial fibrillation was 2.21 (95% confidence interval 1.15-4.23, P = 0.02) in patients with new-onset hypertension versus those with previous hypertension. The association was even stronger in those aged ≥ 75 years (hazard ratio 2.70, 95% confidence interval 1.11-6.56, P = 0.03). In patients with previous hypertension, curvilinear association (P for non-linear trend = 0.04) was observed between duration of hypertension and the risk of incident atrial fibrillation, with a higher risk in short- and long-term than mid-term duration of hypertension. Our study showed a significant association between new-onset hypertension and the incidence of atrial fibrillation in elderly Chinese. In an elderly Chinese population with previous and new-onset hypertension, we found that the new-onset hypertension during follow-up, compared with previous hypertension, was associated with a significantly higher risk of incident atrial fibrillation. In patients with previous hypertension, curvilinear association was observed between duration of hypertension and the risk of incident atrial fibrillation, with a higher risk in short- and long-term than mid-term duration of hypertension.

Life and disease status of patients with Parkinson's disease during and after zero-COVID in China: an online survey.

BACKGROUND: Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. METHODS: This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. RESULTS: A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%). CONCLUSIONS: The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.

Scalable production of recombinant three-finger proteins: from inclusion bodies to high quality molecular probes.

BACKGROUND: The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult. RESULTS: We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography. CONCLUSIONS: Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications.

Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases: Mechanisms and future perspectives.

Pancreatitis and pancreatic cancer (PC) stand as the most worrisome ailments affecting the pancreas. Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases, yet their true nature continues to elude their grasp. Within this realm, oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC. Excessive accumulation of reactive oxygen species (ROS) can cause oxidative stress, and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides (NOX). NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells, activate pancreatic stellate cells, and mediate macrophage polarization. Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis, creating an oxidative microenvironment that can cause abnormal apoptosis, epithelial to mesenchymal transition and genomic instability. Therefore, understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases. In this review, we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders, aiming to provide novel insights into understanding the mechanisms underlying these diseases.

Laser-Induced Skin-like Flexible Pressure Sensor for Artificial Intelligence Speech Recognition.

Skin-like flexible pressure sensors with good sensing performance have great application potential, but their development is limited owing to the need for multistep, high-cost, and low-efficiency preparation processes. Herein, a simple, low-cost, and efficient laser-induced forming process is proposed for the first time to prepare a skin-like flexible piezoresistive sensor. In the laser-induced forming process, based on the photothermal effect of graphene and the foaming effect of glucose, a skin-like polydimethylsiloxanes (PDMS) film with porous structures and surface protrusions is obtained by using infrared laser irradiation of the glucose/graphene/PDMS prepolymer film. Further, based on the skin-like PDMS film with a graphene conductive layer, a new skin-like flexible piezoresistive sensor is obtained. Due to the stress concentration caused by the surface protrusions and the low stiffness caused by the porous structures, the flexible piezoresistive sensor realizes an ultrahigh sensitivity of 1348 kPa-1 at 0-2 kPa, a wide range of 200 kPa, a fast response/recovery time of 52 ms/35 ms, and good stability over 5000 cycles. The application of the sensor to the detection of human pulses and robot clamping force indicates its potential for health monitoring and soft robots. Furthermore, in combination with the neural network (CNN) algorithm in artificial intelligence technology, the sensor achieves 95% accuracy in speech recognition, which demonstrates its great potential for intelligent wearable electronics. Especially, the laser-induced forming process is expected to facilitate the efficient, large-scale preparation of flexible devices with multilevel structures.

Zero-dimensional hybrid tin halides with stable broadband light emissions.

Considering the instability and toxicity of 3D Pb-based perovskite nanocrystals, lead-free low-dimensional organic-inorganic hybrid metal halides have attracted widespread attention as potential substitutes. Herein, two new tin-based 0D halides [H4BAPP]SnBr5·Br and [H4BAPP]SnCl5·Cl·H2O (BAPP = 1,4-bis(3-aminopropyl)piperazine) were synthesized successfully based on [SnX5]3- as an emission center. Typically, [H4BAPP]SnBr5·Br and [H4BAPP]SnCl5·Cl·H2O display broadband yellow and yellow-green light emissions originating from the radiative recombination of self-trapped excitons (STEs). The photoluminescence quantum yields (PLQYs) of the two compounds were calculated to be 19.27% and 2.36%, respectively. Furthermore, the excellent chemical and thermal stability and broadband light emissions reveal their potential application in solid-state white lighting diodes.

Exploring 0D lead-free metal halide with highly efficient blue light emission and high-sensitivity photodetection.

Environmentally friendly and highly efficient blue luminescent materials are an unremitting pursuit in the optoelectronic field. Herein, we assembled a new 0D lead-free metal halide of (F-PPA)ZnBr4, which exhibits narrow blue light emission with a remarkable PLQY of 50.15%, high stability and high detection sensitivity toward UV light. These results indicate the potential for the application of low-dimensional zinc-based halides in multiple optoelectronic devices.

Prevalence, clinical characteristics and treatment outcomes of oxyntic gland neoplasm: a single-center retrospective study.

BACKGROUND: Oxyntic gland neoplasm (OGN) is a rare subtype of gastric cancer. The aim of this study is to evaluate the prevalence, clinicopathological features, effectiveness and safety of endoscopic treatment, as well as the prognosis of OGN. METHODS: We retrospectively analyzed the data of patients pathologically diagnosed with OGN at our hospital from November 1, 2019 to May 1, 2023. RESULTS: A total of 36 patients with 45 lesions were identified, resulting in a disease frequency of 0.047% (36/76,832). The mean age was 55.0 ± 7.5 years, with a male-to-female ratio of about 1:1.12. Most lesions were ≤10 mm in size (84.4%), located in the upper third of the stomach (73.3%), exhibited slight elevation (75.5%), appeared whitish (55%), had dilated blood vessels on the surface (75.5%). 16 and 21 lesions were treated by precutting endoscopic mucosal resection (EMR-P) and endoscopic submucosal dissection (ESD), respectively. No significant differences were found between EMR-P and ESD in terms of en bloc resection rate (100% vs 100%, p = 1.000), complete resection rate (100% vs 90.5%, p = 0.495), and curative resection rate (93.8% vs 90.5%, p = 1.000). No complications such as bleeding and perforation were observed. No recurrence or metastasis was observed during the follow-up period. CONCLUSIONS: OGN is a rare tumor with unique clinical, endoscopic, and pathological characteristics. EMR-P and ESD are deemed safe and effective for treating OGNs. The relatively faster and easier EMR-P seems at least non-inferior to ESD, especially for removal of smaller OGNs. The overall prognosis is favorable.

Efficacy of Chemoimmunotherapy versus Chemotherapy for Gastric Cancer: A Meta-Analysis of Survival Outcomes.

BACKGROUND: Gastric cancer has been traditionally treated with chemotherapy as the primary mode of treatment. However, recent studies have shown that chemoimmunotherapy is also effective and, in some cases, better than chemotherapy treatment. Current study aimed to find the efficacy of chemoimmunotherapy versus chemotherapy in the treatment of gastric cancer. METHODS: Using electronic databases, including PubMed, Embase, and EBSCO, a thorough literature search was carried out for the years 2006 to 2023. The search strategy was designed to identify relevant studies based on chemoimmunotherapy and chemotherapy intervention, and the search was conducted using appropriate keywords and MeSH terms. The retrieved studies were screened for relevance based on their titles, abstracts, and full texts. The studies' inclusion criteria were predefined, and the selected studies were then subjected to a quality assessment using GradePro GDT. The data from selected studies were extracted and analyzed using Revman version 5.4. RESULTS: The study found that chemoimmunotherapy treatment resulted in a significant improvement in overall survival (OS) with a risk ratio (RR) of 1.54 and a 95% Confidence Interval (CI) of 1.25 to 1.89. The overall effect was also found to be significant, with a p-value of less than 0.001. Furthermore, we also observed an improvement in the 1-year, 3-year, and 5-year survival rates with risk ratio (RR) of 1.09 (95% CI: 1.01, 1.17), 1.43 (95% CI: 1.28, 1.60), and 1.59 (95% CI: 1.10, 2.30), respectively. In addition, it's also found that chemoimmunotherapy treatment also resulted in an improvement in DFS with an RR of 1.94 and a 95% CI of 1.44 to 2.59. Overall, these results suggest that chemoimmunotherapy treatment can be an effective approach in comparison to chemotherapy for improving overall survival and disease-free survival in the studied population. CONCLUSION: This study comparing chemoimmunotherapy versus chemotherapy for gastric cancer showed that both treatments were effective, but chemoimmunotherapy had more significant efficacy. To support these results, additional studies with a large sample size and a longer follow-up time are required.

A 0D hybrid lead-free halide with near-unity photoluminescence quantum yield toward multifunctional optoelectronic applications.

Zero-dimensional (0D) hybrid metal halides have emerged as highly efficient luminescent materials, but integrated multifunction in a structural platform remains a significant challenge. Herein, a new hybrid 0D indium halide of (Im-BDMPA)InCl6·H2O was designed as a highly efficient luminescent emitter and X-ray scintillator toward multiple optoelectronic applications. Specifically, it displays strong broadband yellow light emission with near-unity photoluminescence quantum yield (PLQY) through Sb3+ doping, acting as a down-conversion phosphor to fabricate high-performance white light emitting diodes (WLEDs). Benefiting from the high PLQY and negligible self-absorption characteristics, this halide exhibits extraordinary X-ray scintillation performance with a high light yield of 55 320 photons per MeV, which represents a new scintillator in 0D hybrid indium halides. Further combined merits of a low detection limit (0.0853 µGyair s-1), ultra-high spatial resolution of 17.25 lp per mm and negligible afterglow time (0.48 ms) demonstrate its excellent application prospects in X-ray imaging. In addition, this 0D halide also exhibits reversible luminescence off-on switching toward tribromomethane (TBM) but fails in any other organic solvents with an ultra-low detection limit of 0.1 ppm, acting as a perfect real-time fluorescent probe to detect TBM with ultrahigh sensitivity, selectivity and repeatability. Therefore, this work highlights the multiple optoelectronic applications of 0D hybrid lead-free halides in white LEDs, X-ray scintillation, fluorescence sensors, etc.

The effect of increasing the gaps between the front teeth on torque and intrusion control of the incisors for anterior retraction with clear aligners: a prospective study.

OBJECTIVE: To investigate the effect of sequential distalization on increasing gaps in the maxillary anterior teeth, focusing on the control of torque and three-dimensional teeth movement during anterior retraction with clear aligners in extraction cases. METHODS: We recruited 24 patients who were undergoing extraction bilateral maxillary first premolars with clear aligners. According to a predetermined increment in the spaces between the maxillary anterior teeth, the patients were divided into three groups: those with no gap (9 cases), a 0.5 mm gap (6 cases) and a 1.0 mm gap (9 cases). In each group, a 2.0 mm en-mass retraction was applied on the anterior teeth. Plaster casts of the upper full dentition were obtained both before and after a 2 mm retraction. The palatal folds were used to overlap each pair of models. The three-dimensional movement of the teeth and the change of torque for the anterior teeth were subsequently analyzed using Geomagic Studio 2014 software. RESULTS: The change in torque in the groups with added gaps was significantly smaller than that in the group with no gaps (P < 0.05). There was no significant difference in this respect when comparing the group with a 0.5 mm gap added to the group with a 1.0 mm gap was added (P > 0.05). In the labial-lingual and vertical directions, the displacements of the central and lateral incisors were smaller in the groups with additional gaps compared to those in the groups without gaps (P < 0.05). However, there was no significant difference observed when comparing the group with a 0.5 mm added gap to the group with a 1.0 mm added gap (P > 0.05). Then, a comparison was made between the displacement of the second premolar to the second molar in the mesial-distal direction across all groups. The study revealed that the anchorage molars in the group without gaps demonstrated significantly smaller displacement compared to those in the group with additional gaps (P < 0.05). CONCLUSION: Advantages were observed in controlling the torque of the anterior teeth and achieving a desired pattern closer to normal bodily movement by sequentially distalizing the maxillary anterior teeth gaps. Increasing the gaps between the maxillary anterior teeth also resulted in improved control of the vertical direction of the anterior teeth. However, this retraction strategy necessitates substantial protection of the anchorage molars.

High-Sensitivity and Wide-Range Flexible Ionic Piezocapacitive Pressure Sensors with Porous Hemisphere Array Electrodes.

The development of high-performance flexible pressure sensors with porous hierarchical microstructures is limited by the complex and time-consuming preparation processes of porous hierarchical microstructures. In this study, a simple modified heat curing process was first proposed to achieve one-step preparation of porous hemispherical microstructures on a polydimethylsiloxane (PDMS) substrate. In this process, a laser-prepared template was used to form surface microstructures on PDMS film. Meanwhile, the thermal decomposition of glucose monohydrate additive during heat curing of PDMS led to the formation of porous structures within PDMS film. Further, based on the obtained PDMS/CNTs electrodes with porous hemisphere array and ionic polymer dielectric layers, high-performance ionic piezocapacitive sensors were realized. Under the synergistic effect of the low-stiffness porous hemisphere microstructure and the electric double layer of the ionic polymer film, the sensor based on an ionic polymer film with a 1:0.75 ratio of P(VDF-HFP):[EMIM][TFSI] not only achieves a sensitivity of up to 106.27 kPa-1 below 3 kPa, but also has a wide measurement range of over 400 kPa, which has obvious advantages in existing flexible piezocapacitive sensors. The rapid response time of 110 s and the good stability of 2300 cycles of the sensor further elucidate its practicality. The application of the sensor in pulse monitoring, speech recognition, and detection of multiple dynamic loads verifies its excellent sensing performance. In short, the proposed heat curing process can simultaneously form porous structures and surface microstructures on PDMS films, greatly simplifying the preparation process of porous hierarchical microstructures and providing a simple and feasible way to obtain high-performance flexible pressure sensors.

Near-Unity Green Luminescent Hybrid Manganese Halides as X-ray Scintillators.

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

Water extract of earthworms mitigates mouse liver fibrosis by potentiating hepatic LKB1/Nrf2 axis to inhibit HSC activation and hepatocyte death.

ETHNOPHARMACOLOGICAL RELEVANCE: When left untreated, liver fibrosis (LF) causes various chronic liver diseases. Earthworms (Pheretima aspergillum) are widely used in traditional medicine because of their capacity to relieve hepatic diseases. AIM OF THE STUDY: This study aimed to explore the anti-LF effects of water extract of earthworms (WEE) and the underlying molecular mechanisms. MATERIALS AND METHODS: A CCl4-induced mouse model of LF was used to study the impact of WEE on LF in vivo. The anti-LF activity of WEE in mice was compared with that of silybin, which can be clinically applied in LF intervention and was used as a positive control. Activation of LX-2 hepatic stellate cells (HSCs) and apoptosis and ferroptosis of AML-12 hepatocytes induced by TGFß1 were used as in vitro models. RESULTS: WEE drastically improved LF in mice. WEE reduced markers of activated HSCs in mice and inhibited TGFß1-induced activation of LX-2 HSCs in vitro. Additionally, WEE suppressed CCl4-induced apoptosis and ferroptosis in mouse hepatocytes. Mechanistically, WEE induced Nrf2 to enter the nuclei of the mouse liver cells, and the hepatic levels of Nrf2-downstream antioxidative factors increased. LKB1/AMPK/GSK3ß is an upstream regulatory cascade of Nrf2. In the LF mouse model, WEE increased hepatic phosphorylated LKB1, AMPK, and GSK3ß levels. Similar results were obtained for the LX-2 cells. In AML-12 hepatocytes and LX-2 HSCs, WEE elevated intracellular Nrf2 levels, promoted its nuclear translocation, and inhibited TGFß1-induced ROS accumulation. Knocking down LKB1 abolished the impact of WEE on the AMPK/GSK3ß/Nrf2 cascade and eliminated its protective effects against TGFß1. CONCLUSIONS: Our findings reveal that WEE improves mouse LF triggered by CCl4 and supports its application as a promising hepatoprotective agent against LF. The potentiation of the hepatic antioxidative AMPK/GSK3ß/Nrf2 cascade by activating LKB1 and the subsequent suppression of HSC activation and hepatocyte apoptosis and ferroptosis are implicated in WEE-mediated alleviation of LF.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

The role of physical activity on healthcare utilization in China.

BACKGROUND: Evidence on the role of physical activity (PA) on healthcare utilization and expenditure is limited in China. We aimed to examine the association between the total physical activity (TPA) per week, healthcare service use and expenditure. METHODS: We extracted the data from China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, and 2015. Participants more than 50 years old who completed the follow-up for the three waves were enrolled. We converted the volume of vigorous physical activity (VPA) into an equivalent volume of moderate physical activity (MPA) and calculated the TPA per week for each participant. 12,927 of the 17,708 participants in CHARLS were included in our analysis. More than one-third of participants over 50 years old never participate in any moderate or intensity activity, and the median of self-reported moderate or intensity PA was about 525 (IQR 0-1680) MET-minutes per week in 2015. RESULTS: Compared to inactive subjects, the highest level of TPA was significantly related to the decreased risk number of inpatient visits (IRR: 0.58; 95% CI:0.50-0.67, p < 0.001), inpatient hospital days (IRR: 0.60; 95% CI: 0.42-0.84, p < 0.01), healthcare expenditure (IRR: 0.71; 95% CI: 0.65-0.79, p < 0.001) and catastrophic health expenditures (OR: 0.57; 95% CI: 0.45-0.72, p < 0.001) after adjusting for covariates. CONCLUSIONS: Engaging in moderate-to-vigorous PA may drive a potential decrease in healthcare utilization, healthcare expenditure and household financial risk with a dose-response relationship in China, and some possible policy implications in public health may be considered to promote exercise in the middle-aged and elderly to reduce the medical burden on individuals and healthcare systems.