Immune checkpoint inhibitor-associated new-onset hypophysitis: a retrospective analysis using the FAERS.

BACKGROUND: Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated hypophysitis (ICI-hypophysitis) using data from the FAERS, and the risk factors of prognosis were explored. METHODS: In this retrospective study, all cases of newly-diagnosed hypophysitis associated with FDA approved ICIs from 1st January 2007 to 31st December 2022 were accumulated using FAERS. Demographic data including age, sex, body weight, the prognosis of cases, and other co-occurred endocrinopathies induced by ICIs were analyzed and compared between different subgroups of immunotherapy. RESULTS: The reporting frequency of ICI-hypophysitis was 1.46% (2343/160089). Patients on the combination therapy had higher risk of hypophysitis reporting, followed by anti-CTLA-4 agent compared with other monotherapies (p < 0.001). Male subjects displayed higher reporting risk of ICI-hypophysitis (p = 0.015). Patients on anti-PD-1 therapy or the combination therapy showed higher occurrence rate of type 1 diabetes (anti-PD-1 vs. anti-PD-L1 vs. anti-CTLA-4 vs. combination therapy, 4.2% vs. 0.7% vs. 0.3% vs. 8.4%, p < 0.001). The occurrence rate of new-onset thyroid diseases in patients receiving combination therapy was higher than anti-PD-1 monotherapy (12.3% vs. 8.4%, p = 0.010). Elder age, lung cancer, and renal cancer emerged to be positively associated with severe clinical outcomes [>65 years, OR 1.042, 95%CI (1.022-1.063), p < 0.001; lung cancer, OR 1.400, 95%CI (1.019-1.923), p = 0.038; renal cancer, OR 1.667, 95%CI (1.153-2.412), p = 0.007]. Anti-CTLA-4 monotherapy was discovered to be a protective factor of severe outcomes [OR 0.433, 95%CI (0.335-0.558), p < 0.001]. Female sex and co-occurrence of ICI-related diabetes exhibited lower risk of death [female, OR 0.571, 95%CI (0.361-0.903), p = 0.017; diabetes, OR 0.090, 95%CI (0.016-0.524), p = 0.007]. CONCLUSIONS: ICI-induced hypophysitis is male-predominant irAE, most commonly seen in patients on anti-CTLA-4 mono- or combination therapy. Awareness among clinicians is critical when patients with elder age, lung or renal cancer develop hypophysitis, which indicates poor clinical outcomes. Female sex, anti-CTLA-4 monotherapy and co-occurrence of ICI-related diabetes are protective risk factors for poor prognosis.

Exposure to a mixture of metal(loid)s and sleep quality in pregnant women during early pregnancy: A cross-sectional study.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

Bioinspired High-Linearity, Wide-Sensing-Range Flexible Stretchable Bioelectronics Based on MWCNTs/GR/Nd2Fe14B/PDMS Nanocomposites for Human-Computer Interaction and Biomechanics Detection.

In recent years, flexible and stretchable strain sensors have emerged as a prominent area of research, primarily due to their remarkable stretchability and extremely low strain detection threshold. Nevertheless, the advancement of sensors is currently constrained by issues such as complexity, high costs, and limited durability. To tackle the aforementioned issues, this study introduces a lepidophyte-inspired flexible, stretchable strain sensor (LIFSSS). The stretchable bioelectronics composites were composed of multiwalled carbon nanotubes, graphene, neodymium iron boron, and polydimethylsiloxane. Unique biolepidophyted microstructures and magnetic conductive nanocomposites interact with each other through synergistic interactions, resulting in the effective detection of tensile strain and magnetic excitation. The LIFSSS exhibits a 170% tensile range, a linearity of 0.99 in 50-170% strain (0.96 for full-scale range), and a fine durability of 7000 cycles at 110% tensile range. The sensor accurately detects variations in linear tensile force, human movement, and microexpressions. Moreover, LIFSSS demonstrates enhanced efficacy in sign language recognition for individuals with hearing impairments and magnetic grasping for robotic manipulators. Hence, the LIFSSS proposed in this study shows potential applications in various fields, including bioelectronics, electronic skin, and physiological activity monitoring.

Study on the clinical value of the wearable foetal electrocardiogram monitoring system.

BACKGROUND: Electronic foetal monitoring (EFM), a method to monitor foetal intrauterine conditions and foetal reserve capacity, is the most extensively used intrauterine monitoring technology in obstetrics. OBJECTIVE: This study aims to compare the Thoth wearable foetal electrocardiogram (foetal ECG [FECG]) monitoring system with a traditional Doppler foetal heart monitoring system before labour to investigate their respective values in clinical application. METHODS: A total of 393 pregnant women admitted to our hospital between 2020 and 2022 participated in this study. They were recruited using the convenience sampling method. We employed a paired design to assess the confusion rate, trend overlap, and foetal heart rate/ECG monitoring consistency, whereas a completely randomised design was used to measure pregnancy outcome indicators. The participants were divided into two groups using a random number table: the Thoth group (n= 196) and the traditional Doppler group (n= 197). Each group was monitored using the corresponding system. RESULTS: The Thoth monitor demonstrated a lower confusion rate compared with the traditional Doppler monitor (0.25% vs 2.04%; χ2= 5.508, P= 0.019). The trend overlap in foetal heart rates was consistently 100%, with 91.2% of readings showing a consistency rate of ⩾ 95%. Additionally, the Thoth monitor recorded a higher cumulative interruption time in the foetal heart rate curve (12.13 ± 2.22 vs 21.02 ± 2.34; t= 18.471, P< 0.001) and more abnormal ECGs (21.21 ± 4.32 vs 18.21 ± 2.91; t= 7.582, P< 0.001) than the traditional Doppler system. CONCLUSION: The Thoth wearable FECG monitor offers several advantages over the traditional Doppler foetal heart monitoring system. These include a reduced confusion rate, more accurate data collection, a lower rate of clinical misjudgement, reduced workload for medical staff, and enhanced comfort during vaginal delivery. The rates of emergency caesarean sections and neonatal asphyxia in the Thoth group were marginally lower than those in the Doppler group, which may be attributed to issues such as ECG disconnection or interference from the maternal heart rate.

Urinary concentrations of mineral elements and their predictors in pregnant women in Jinan, China.

BACKGROUND: The essential mineral elements play important roles in proper growth, development and maintenance of physiological homeostasis of an organism. Women are at greater risk of mineral deficiency during pregnancy. However, the predictors of mineral element levels in pregnant women remain unclear. This study was conducted to determine the urinary levels of calcium (Ca), iron (Fe), copper (Cu), manganese (Mn) and selenium (Se) in women during early pregnancy and to explore the predictors of urinary exposure to each mineral element and high co-exposure to mineral element mixture. METHODS: 298 pregnant women in first trimester were recruited when they attended antenatal care in a hospital in Jinan, Shandong Province, China. We collected their spot urine samples and questionnaire data on their sociodemographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment. The concentrations of Ca, Fe, Cu, Mn and Se in all urine samples were measured. LASSO regression, multiple linear regression and binary logistic regression were used to analyze the predictors affecting mineral element levels. RESULTS: The geometric means of creatinine-corrected Ca, Fe, Cu, Mn and Se concentrations were 99.37 mg/g, 1.75 µg/g, 8.97 µg/g, 0.16 µg/g and 16.83 µg/g creatinine, respectively. Factors that influenced the concentrations of individual mineral element were as follows: (1) Se and Ca concentrations increased with maternal age; (2) women taking tap water as family drinking water had higher Ca levels and those taking polyunsaturated fatty acids intermittently had higher Cu levels; (3) Fe was adversely related to consumption frequency of barbecued foods; (4) Pregnant women with more frequent consumption of shellfish/shrimp/crab and living near green spaces or parks had higher Mn exposure, and those with higher frequency of meat consumption had lower Mn exposure. In addition, maternal age and the frequency of egg consumption were associated with odds of exposure to a mixture of high Ca, Fe, Cu and Se. CONCLUSIONS: The pregnant women in this study had comparable concentrations of urinary Cu and Se but lower concentrations of Ca, Fe and Mn compared with those in other areas. Predictors of urinary mineral elements included maternal age (Se and Ca), type of domestic drinking water (Ca), consumption frequency of barbecued food (Fe), polyunsaturated fatty acid use (Cu), the presence of urban green spaces or parks near the home and frequency of meat and shellfish/shrimp/crab intake (Mn). Moreover, maternal age and egg consumption frequency were significant predictors of high-level co-exposure to urinary Ca, Fe, Cu and Se.

Mechanistic modeling of alarm signaling in seed-harvester ants.

Ant colonies demonstrate a finely tuned alarm response to potential threats, offering a uniquely manageable empirical setting for exploring adaptive information diffusion within groups. To effectively address potential dangers, a social group must swiftly communicate the threat throughout the collective while conserving energy in the event that the threat is unfounded. Through a combination of modeling, simulation, and empirical observations of alarm spread and damping patterns, we identified the behavioral rules governing this adaptive response. Experimental trials involving alarmed ant workers (Pogonomyrmex californicus) released into a tranquil group of nestmates revealed a consistent pattern of rapid alarm propagation followed by a comparatively extended decay period [1]. The experiments in [1] showed that individual ants exhibiting alarm behavior increased their movement speed, with variations in response to alarm stimuli, particularly during the peak of the reaction. We used the data in [1] to investigate whether these observed characteristics alone could account for the swift mobility increase and gradual decay of alarm excitement. Our self-propelled particle model incorporated a switch-like mechanism for ants' response to alarm signals and individual variations in the intensity of speed increased after encountering these signals. This study aligned with the established hypothesis that individual ants possess cognitive abilities to process and disseminate information, contributing to collective cognition within the colony (see [2] and the references therein). The elements examined in this research support this hypothesis by reproducing statistical features of the empirical speed distribution across various parameter values.

Exploring the Correlation Between Varied Serum Iodine Nutritional Levels and Anti-Thyroglobulin Antibodies.

Iodine deficiency results in elevated thyroglobulin (Tg) concentrations, with high iodine Tg being more immunogenic than low iodine Tg. The study investigated the correlation between serum iodine concentration and thyroglobulin autoantibody (TgAb) levels across diverse iodine nutritional statuses as determined by urine iodine concentration (UIC). Demographic information was collected from 1,482 participants through a questionnaire. Blood and spot urine were collected to measure thyroid-stimulating hormone (TSH), TgAb, thyroid anti-peroxidase antibody (TPOAb), serum iodine (SIC), serum non-protein-bound iodine (snPBI), urine iodine (UIC), creatinine (UCr). The median UIC and SIC were 146.5 µg/L and 74.9 µg/L, respectively. A linear relationship was observed between SIC, snPBI, and serum-protein-bound iodine (sPBI) (P < 0.001). The 90% reference intervals for SIC, snPBI, and sPBI were 50.7-120.7 µg/L, 21.9-52.9 µg/L, and 19.7-77.9 µg/L, respectively. The prevalence of elevated TgAb levels was significantly higher in women than in men (P < 0.001). Both low and high levels of snPBI and sPBI were associated with an increased risk of elevated TgAb levels. In women, the risk of positive TgAb in the group below the reference value of snPBI (OR = 2.079, 95%CI: 1.166, 3.705) and sPBI (OR = 2.578, 95%CI: 1.419, 4.684) was higher. In men, the risk of positive TgAb in the group below the reference value of SIC was higher (OR = 3.395, 95%CI: 1.286, 8.962). Iodine might exert an influence on TgAb levels through its binding to proteins, primarily Tg, thereby altering the iodine content of Tg. The interplay of gender factors further enhanced the risk of TgAb emergence.

Flexible Strain Sensor Based on Nickel Microparticles/Carbon Black Microspheres/Polydimethylsiloxane Conductive Composites for Human Motion Detection.

Herein, we report a dual-functional flexible sensor (DFFS) using a magnetic conductive polymer composed of nickel (Ni), carbon black (CB), and polydimethylsiloxane (PDMS). The material selection for the DFFS utilizes the excellent elasticity of the PDMS matrix and the synergistic interaction between Ni and CB. The DFFS has a wide strain range of 0-170%, a high sensitivity of 74.13 (140-170%), and a low detection limit of 0.3% strain. The DFFS based on superior performance can accurately detect microstrain/microvibration, oncoming/contacting objects, and bicycle riding speed. Additionally, the DFFS can be used for comprehensive monitoring of human movements. Therefore, the DFFS of this work shows significant value for implementation in intelligent wearable devices and noncontact intelligent control.

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain.

INTRODUCTION: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group. CONCLUSIONS: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04094662.

Electrochemical Oxidation Enables Radical Dearomative Spiroannulation to 2H-Spiro[benzofuran-3,9'-fluoren]-2-one.

Developing pragmatic strategies for accessing functional benzofuran-2-ones from 3-([1,1'-biphenyl]-2-yl)benzofuran remains an enduring challenge. Herein, we have achieved a highly discriminating electrochemical oxidative dearomative spiroannulation of 3-([1,1'-biphenyl]-2-yl)benzofuran, culminating in the synthesis of 2H-spiro[benzofuran-3,9'-fluoren]-2-one derivatives. By harnessing the electrophilic intermediates of benzofuryl radical cations supported by DFT calculations, we attain exceptional regioselectivity while eliminating the need for stoichiometric oxidants. Mechanistic investigations reveal a sequence of events involving the benzofuran radical cation, encompassing the capture of H2O, nucleophilic arene attack, and subsequent deprotonation, ultimately yielding the final benzofuran-2-ones.

Nanocellulose-Enhanced, Easily Processable Cellulose-Based Flexible Pressure Sensor for Wearable Epidermal Sensing.

Flexible pressure sensors (FPSs) based on biomass materials have gained considerable attention for their potential in wearable electronics, human-machine interaction, and environmental protection. Herein, flexible silver nanowire-dual-cellulose paper (SNdCP) containing common cellulose fibers, cellulose nanofibers (CNFs), and silver nanowires (AgNWs) for FPSs was assembled by a facile papermaking strategy. Compared with bacterial cellulose (BC) and cellulose nanocrystals (CNCs), CNFs possess better dimensions and reinforcement, which enables the composite paper to exhibit better mechanical properties (tensile stress of 164.65 MPa) and electrical conductivity (11600 S·m-1), providing more possibilities for FPSs. Benefiting from these advantages, we construct an easily processable and sensitive human-interactive FPS based on a composite paper with high sensitivity (0.050 kPa-1), fast response/recovery time (158/95 ms), and exceptional stability (>1000 bending cycles), capable of responding to finger motions, voice recognition, and human pulses; through further employment as the array unit and a control circuit, the observed highly adaptive mechano-electric transformability and functions are well maintained. Overall, a facile and versatile strategy with the potential to provide clues for the fabrication of cellulose-based FPSs with outstanding performance was introduced.

Dynamics of Information Flow and Task Allocation of Social Insect Colonies: Impacts of Spatial Interactions and Task Switching.

Models of social interaction dynamics have been powerful tools for understanding the efficiency of information spread and the robustness of task allocation in social insect colonies. How workers spatially distribute within the colony, or spatial heterogeneity degree (SHD), plays a vital role in contact dynamics, influencing information spread and task allocation. We used agent-based models to explore factors affecting spatial heterogeneity and information flow, including the number of task groups, variation in spatial arrangements, and levels of task switching, to study: (1) the impact of multiple task groups on SHD, contact dynamics, and information spread, and (2) the impact of task switching on SHD and contact dynamics. Both models show a strong linear relationship between the dynamics of SHD and contact dynamics, which exists for different initial conditions. The multiple-task-group model without task switching reveals the impacts of the number and spatial arrangements of task locations on information transmission. The task-switching model allows task-switching with a probability through contact between individuals. The model indicates that the task-switching mechanism enables a dynamical state of task-related spatial fidelity at the individual level. This spatial fidelity can assist the colony in redistributing their workforce, with consequent effects on the dynamics of spatial heterogeneity degree. The spatial fidelity of a task group is the proportion of workers who perform that task and have preferential walking styles toward their task location. Our analysis shows that the task switching rate between two tasks is an exponentially decreasing function of the spatial fidelity and contact rate. Higher spatial fidelity leads to more agents aggregating to task location, reducing contact between groups, thus making task switching more difficult. Our results provide important insights into the mechanisms that generate spatial heterogeneity and deepen our understanding of how spatial heterogeneity impacts task allocation, social interaction, and information spread.

Predictors of urinary heavy metal concentrations among pregnant women in Jinan, China.

BACKGROUND: Toxic heavy metal exposure and insufficiency or excess of essential heavy metals may have negative effects on pregnant women's health and fetal growth. To date, the predictors of pregnant women's heavy metal exposure levels remain unclear and vary with different regions. The study intended to explore potential predictors of exposure to heavy metals individually and high co-exposure to heavy metal mixtures. METHODS: We recruited 298 pregnant women in first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected spot urine samples and questionnaire data on their demographic characteristics, lifestyle habits, consumption of food and dietary supplement, and residential environment. All urine samples were analyzed for seven heavy metals: cobalt (Co), molybdenum (Mo), strontium (Sr), arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg). RESULTS: Factors associated with single heavy metal concentration were as follows: a) urinary As, Sr and Cd increased with women's age respectively; b) pregnant women with higher monthly household income per capita had lower Sr and Mo levels; c) pregnant women with intermittent folic acid supplementation and those not taking tap water as domestic drinking water had lower Sr concentrations; d) Cd was positively linked with consumption frequency of rice; e) Hg was adversely related to consumption frequency of egg and the women who took purified water as domestic drinking water had lower Hg exposure. In addition, pregnant women's age was positively associated with odds of high co-exposure to Co, As, Sr, Mo, Cd and Pb; while those with an educational level of college had lower odds of high exposure to such a metal mixture compared with those whose educational levels were lower than high school. CONCLUSION: Predictors of single urinary heavy metal concentration included pregnant women's age (As, Sr and Cd), monthly household income per capita (Sr and Mo), folic acid supplementation (Sr), rice consumption frequency (Cd), egg consumption frequency (Hg) and the type of domestic drinking water (Sr and Hg). Pregnant women with older age, lower educational level tended to have high co-exposure to Co, As, Sr, Mo, Cd and Pb.

Optimized Intermediates Adsorption Configuration on Co-Doped Fe2 P@NiP2 Heterojunction Interface for Enhanced Electrocatalytic Nitrate-To-Ammonia Conversion.

The extraction of ammonia (NH3 ) through electrocatalytic nitrate reduction reaction (NO3 - RR) represents a sustainable avenue in NH3 generation and utilization. However, the catalytic efficiency of the NO3 - RR is hindered by the sluggish kinetics. This study first theoretically found that phosphide-based heterostructure can alter the adsorption structure of intermediates in the nitrate-to-ammonia process, thereby achieving precise regulation of the energy barrier in the rate-determining step. Based on theoretical design, a novel Co-doped Fe2 P@NiP2 heterojunction catalyst is successfully synthesized, which deliver a notable NH3 yield rate of 0.395 mmol h-1  cm-2 at -0.7 V versus RHE, as well as a remarkable ammonia Faraday efficiency of 97.2% at -0.6 V versus RHE. Experimental and theoretical results further confirm that redistributing electrons and shifting the center of the d-band upwards through interfacial doping modulate intermediates adsorption strength and inhibition of hydrogen evolution, leading to excellent performance in NO3 - -to-NH3 . Further integrating the Co-Fe2 P@NiP2 catalyst into a Zn-nitrate battery exhibits a substantial voltage output of 1.49 V and a commendable power density of 13.2 mW cm-2 . The heteroatom-doped heterojunction strategy provides a versatile route for developing advanced catalysts, thereby broadening the horizons of electrocatalytic methodologies for nitrate reduction and ammonia synthesis.

Three-Dimensional Vanadium and Nitrogen Dual-Doped Ti3C2 Film with Ultra-High Specific Capacitance and High Volumetric Energy Density for Zinc-Ion Hybrid Capacitors.

Zinc-ion hybrid capacitors (ZICs) can achieve high energy and power density, ultralong cycle life, and a wide operating voltage window, and they are widely used in wearable devices, portable electronics devices, and other energy storage fields. The design of advanced ZICs with high specific capacity and energy density remains a challenge. In this work, a novel kind of V, N dual-doped Ti3C2 film with a three-dimensional (3D) porous structure (3D V-, N-Ti3C2) based on Zn-ion pre-intercalation can be fabricated via a simple synthetic process. The stable 3D structure and heteroatom doping provide abundant ion transport channels and numerous surface active sites. The prepared 3D V-, N-Ti3C2 film can deliver unexpectedly high specific capacitance of 855 F g-1 (309 mAh g-1) and demonstrates 95.26% capacitance retention after 5000 charge/discharge cycles. In addition, the energy storage mechanism of 3D V-, N-Ti3C2 electrodes is the chemical adsorption of H+/Zn2+, which is confirmed by ex situ XRD and ex situ XPS. ZIC full cells with a competitive energy density (103 Wh kg-1) consist of a 3D V-, N-Ti3C2 cathode and a zinc foil anode. The impressive results provide a feasible strategy for developing high-performance MXene-based energy storage devices in various energy-related fields.

Ultrasound-targeted microbubble technology facilitates SAHH gene delivery to treat diabetic cardiomyopathy by activating AMPK pathway.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication with no known cure. In this study, we evaluated the combination of ultrasound-targeted microbubble destruction (UTMD) and cationic microbubbles (CMBs) for cardiac S-adenosyl homocysteine hydrolase (SAHH) gene transfection as potential DCM therapy. Models of high glucose/fat (HG/HF)-induced H9C2 cells and streptozotocin-induced DCM rats were established. Ultrasound-mediated SAHH delivery using CMBs was a safe and noninvasive approach for spatially localized drug administration both in vitro and in vivo. Notably, SAHH overexpression increased cell viability and antioxidative stress and inhibited apoptosis of HG/HF-induced H9C2 cells. Likewise, UTMD-mediated SAHH delivery attenuated apoptosis, oxidative stress, cardiac fibrosis, and myocardial dysfunction in DCM rats. Activation of the AMPK/FOXO3/SIRT3 signaling pathway may be a key mechanism mediating the role of SAHH in regulating myocardial injury. Thus, UTMD-mediated SAHH transfection may be an important advancement in cardiac gene therapy for restoring ventricular function after DCM.

Cationic cellulose nanofibers/chitosan auxiliary-dominated win-win strategy for paper yarn with superior color and physical performances.

The colored and high-saline effluents during the traditional dyeing process poses serious environmental challenge. In our study, an eco-friendly cationic cellulose nano-fiber/chitosan (CCNF/CS) binary versatile auxiliary was designed for the neutral salt-free dyeing and physical enhancement of paper by mixing with pulp simply. Profiting from the rich cationic binding sites of CCNF/CS (Charge density: 3749.67 µmol/g), under near neutral conditions (pH = 6.2), the maximum adsorption capacity of anionic GL (Direct fast turquoise blue GL) on paper with 0.5 % CCNF/CS reached 1865.06 mg/g with a desirable evenness (45.5 % and 92.1 % higher than that of CCNF and NaCl group, respectively), and the dye uptake was up to 97 %. The spontaneous adsorption behavior was aligned with the pseudo-second-order and Langmuir models, with a primary physical mechanism enhanced by chemical forces. The combination of strong electronic attraction, hydrogen bonding, and n-π stacking effects granted CCNF/CS an enhanced proficiency in anionic dye adsorption. In addition, the tensile strength of the resulting paper yarn with 0.5 % CCNF/CS increased to 52.47 MPa under the optimal parameters, deriving from the CCNF/CS-induced inter-fiber cohesion. Overall, our research provided a green promising approach for the innovative neutral salt-free dyeing and mechanical enhancement of paper.

Prusogliptin (DBPR108) monotherapy in treatment-naïve patients with type 2 diabetes: A randomized, double-blind, active and placebo-controlled, phase 3 study.

AIM: This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase-4 inhibitor, in individuals with type 2 diabetes who had not been using glucose-lowering agents regularly for the 8 weeks before the screening period. MATERIALS AND METHODS: In this multicentre, randomized, double-blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24-week double-blind treatment period, followed by a 28-week open-label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24. RESULTS: In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 ± 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were -0.63% (0.04%) for DBPR108, -0.60% (0.07%) for sitagliptin and -0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was -0.61% (95% CI -0.77% to -0.44%), and between DBPR108 and sitagliptin was -0.03% (95% CI -0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non-inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were -0.50% (0.97%) for the DBPR108 group, -0.46% (0.96%) for the sitagliptin group and -0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups. CONCLUSIONS: DBPR108 showed superiority to placebo and non-inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment-naïve patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.

Efficacy and safety of intragastric expandable oral capsules in adults with overweight or obesity: A randomized, double-blind, placebo-controlled trial.

AIM: This trial assessed the efficacy and safety of 2.24 g intragastric expandable capsules twice per day versus placebo for weight management in adults with overweight or obesity. METHODS: This double-blind, placebo-controlled study included adults with a body mass index of at least 24 kg/m2 and no more than 40 kg/m2 . In total, 280 participants were recruited from six hospitals in China and were assigned in a 1:1 ratio to receive 2.24 g oral intragastric expandable capsules or placebo for 24 weeks. Coprimary endpoints were the percentage change in body weight from baseline and the rate of weight reduction of ≥5%, assessed using both the full analysis set and per protocol set. RESULTS: At baseline, the mean body weight was 81.8 kg, and the mean body mass index was 29.4 kg/m2 . The mean body weight change at week 24 was -4.9% with intragastric expandable capsules versus -1.9% with placebo [estimated treatment difference (ETD) -3.0%, 95% confidence interval (CI) -4.1 to -1.9; p < .001] using the full analysis set and -6.1% versus -2.5% (ETD -3.6%, 95% CI -5.0 to -2.3; p < .001), respectively, using the per protocol set. The percentage of participants who had weight loss exceeding 5% was 45.0% in the intragastric expandable capsule group versus 19.7% in the placebo group (ETD 25.3%, 95% CI 14.7-35.9; p < .001) in the full analysis set and 55.9% versus 26.2% (ETD 29.6%, 95% CI 17.1-42.2; p < .001), respectively, in the per protocol set. Waist circumference significantly decreased at week 24 (intragastric expandable capsules vs. placebo: -5.6 ± 8.3 cm vs. -2.9 ± 4.8 cm; p = .003). The most common adverse events associated with the use of intragastric expandable capsules were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), and most were mild and transient. CONCLUSIONS: In this 24-week trial including participants with overweight or obesity, 2.24 g of intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo.