Dynamic intrauterine crosstalk promotes porcine embryo implantation during early pregnancy.

Dynamic crosstalk between the embryo and mother is crucial during implantation. Here, we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium, identifying 4 different lineages in embryos and 13 cell types in the endometrium. Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations, showing development from undifferentiated trophectoderm to polar and mural trophectoderm. Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation. Then, we developed a novel tool, ExtraCellTalk, generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells. These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.

Performance of High-Dose Reclaimed Asphalt Mixtures (RAPs) in Hot In-Place Recycling Based on Balanced Design.

This study endeavors to employ a balanced design methodology, aiming to equilibrate the resistance to rutting and cracking exhibited by hot in-place recycling asphalt mixtures containing a high dose of reclaimed asphalt pavement (RAP). The primary goal is to ascertain the optimal amount of new binder necessary for practical engineering applications, ensuring a balanced rutting and crack resistance performance of recycled asphalt mixtures. The investigation mainly employed wheel-tracking tests and semi-circular bending tests to assess the rutting and cracking performance of recycled asphalt mixtures with a different dose of RAP (in China, it is common to use RAP with 80% and 90% content as additives for preparing hot in-place recycling asphalt mixtures), and varying quantities of new binders (10%, 20%, and 30% of the binder content in the total RAP added). The results indicated that the addition of new binder reduced the resistance to rutting of the recycling asphalt mixtures but improved their resistance to cracking. Furthermore, for the recycling asphalt mixture with 80% RAP content aged for 5 days, the optimal new binder content is 1.52%, while the mixture with 90% RAP content requires 1.23% of new binder. After 10 days of aging, the optimal new binder content for the recycling asphalt mixture with 80% RAP content is 1.55%, while the mixture with 90% RAP content requires 1.28% of new binder.

Taking advantage of the interaction between the sulfoxide and heme cofactor to develop indoleamine 2, 3-dioxygenase 1 inhibitors.

Taking advantage of key interactions between sulfoxide and heme cofactor, we used the sulfoxide as the anchor functional group to develop two series of indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors: 2-benzylsulfinylbenzoxazoles (series 1) and 2-phenylsulfinylbenzoxazoles (series 2). In vitro enzymatic screening shows that both series can inhibit the activity of IDO1 in low micromolar (series 1) or nanomolar (series 2) levels. They also show inhibitory selectivity between IDO1 and tryptophan 2, 3-dioxygenase 2. Interestingly, although series 1 is less potent IDO1 inhibitors of these two series, it exhibited stronger inhibitory activity toward kynurenine production in interferon-γ stimulated BxPC-3 cells. Enzyme kinetics and binding studies demonstrated that 2-sulfinylbenzoxazoles are non-competitive inhibitors of tryptophan, and they interact with the ferrous form of heme. These results demonstrated 2-sulfinylbenzoxazoles as type II IDO1 inhibitors. Furthermore, molecular docking studies supports the sulfoxide being of the key functional group that interacts with the heme cofactor. Compound 22 (series 1) can inhibit NO production in a concentration dependent manner in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and can relieve pulmonary edema and lung injury in LPS induced mouse acute lung injury models.

Boosting Demulsification and Antifouling Capacity of Membranes via an Enhanced Piezoelectric Effect for Sustaining Emulsion Separation.

Traditional superwettable membranes for demulsification of oil/water emulsions could not maintain their separation performance for long because of low demulsification capacity and surface fouling during practical applications. A charging membrane could repel the contaminants for a while, the charge of which would gradually be neutralized during the separation progress. Here, a superhydrophilic piezoelectric membrane (SPM) with sustained demulsification and antifouling capacity is proposed for achieving prolonged emulsion separation, which is capable of converting inherent pulse hydraulic filtration pressure into pulse voltage. A pulse voltage up to -7.6 V is generated to intercept the oil by expediting the deformation and coalescence of emulsified oil droplets, realizing the demulsification. Furthermore, it repels negatively charged oil droplets, avoiding membrane fouling. Additionally, any organic foulants adhering to the membrane undergo degradation facilitated by the generated reactive oxygen species. The separation data demonstrate a 98.85% efficiency with a flux decline ratio below 14% during a 2 h separation duration and a nearly 100% flux recovery of SPM. This research opens new avenues in membrane separation, environmental remediation, etc.

pH Modulation of Super-Assembled Heteromembranes for Sustainable Chiral Sensing.

Enantioselective sensing and separation represent formidable challenges across a diverse range of scientific domains. The advent of hybrid chiral membranes offers a promising avenue to address these challenges, capitalizing on their unique characteristics, including their heterogeneous structure, porosity, and abundance of chiral surfaces. However, the prevailing fabrication methods typically involve the initial preparation of achiral porous membranes followed by subsequent modification with chiral molecules, limiting their synthesis flexibility and controllability. Moreover, existing chiral membranes struggle to achieve coupled-accelerated enantioseparation (CAE). Here, we report a replacement strategy to controllably produce mesoscale and chiral silica-carbon (MCSC) hybrid membranes that comprise chiral pores by interfacial superassembly on a macroporous alumina (AAO) membrane, in which both ion- and enantiomers can be effectively and selectively transported across the membrane. As a result, the heterostructured hybrid membrane (MCSC/AAO) exhibits enhanced selectivity for cations and enantiomers of amino acids, achieving CAE for amino acids with an isoelectric point (pI) exceeding 7. Interestingly, the MCSC/AAO system demonstrates enhanced pH-sensitive enantioseparation compared to chiral mesoporous silica/AAO (CMS/AAO) with significant improvements of 78.14, 65.37, and 14.29% in the separation efficiency, separation factor, and permeate flux, respectively. This work promises to advance the synthesis of two or more component-integrated chiral nanochannels with multifunctional properties and allows a better understanding of the origins of the homochiral hybrid membranes.

Constructing novel hydrated metal molten salt with high self-healing as the anode material for lithium-ion batteries.

Lithium-ion batteries (LIBs) are greatly limited in their practical application because of their poor cycle performance, low conductivity and volume expansion. Herein, molten salts (MSs) FeCl3·6H2O-NMP with low temperature via simple preparation are used as the anode material of LIBs for the first time to break through the bottleneck of LIBs. The good fluidity and high self-healing of FeCl3·6H2O-NMP effectively avoid the collapse and breakage of the structure. Based on this feature, the initial discharge specific capacity reached 770.28 mA h g-1, which was more than twice that of the commercial graphite anode. After 200 cycles at a current density of 100 mA g-1, the specific capacity did not decrease rather it was found to be higher than the initial discharge specific capacity, reaching 867.24 mA h g-1. Besides, the good conductivity of MSs provides convenience for the removal and intercalation of Li+. The active H sites that can combine with lithium ions form LiH and provide capacity for LIBs. Density functional theory (DFT) calculation also provided theoretical proof for the mechanism of LIBs.

Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

PURPOSE: To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. METHODS: Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. RESULTS: Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. CONCLUSION: Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

The trend of radiographic healing after root canal treatment in teeth with apical periodontitis based on cone-beam computed tomography: A 4-year longitudinal study.

OBJECTIVES: The aim of this study was to observe the radiographic healing of periapical lesions after root canal treatment via volumetric measurements based on cone-beam computed tomography (CBCT) over 4 years. METHODS: In total, 162 single-root teeth from patients with chronic periapical periodontitis who underwent primary root canal treatment were included in this retrospective study. Follow-up visits were scheduled at 1, 2, and 4 years after treatment. The volume of radiolucency at pretreatment and follow-up were measured, and the radiographic outcomes were classified into 4 categories: absence, reduction, uncertain or enlargement. Reduction or enlargement was considered when the volumetric change in radiolucency was 20 % or more. RESULTS: During the 4-year follow-up period, 128 teeth were reviewed at least once, including 3 extracted teeth. Of the remaining 125 teeth, the volume of radiolucency was reduced in 116 teeth (90.6 %), uncertain in 5, and enlarged in 4 teeth during 1 to 4 years after treatment. Among the 43 teeth with reduced radiolucency at 1 year after treatment, 42 (97.7 %) had continuing reduced lesions at 4 years. In the 2 teeth with enlarged radiolucency at 1 year, the volume of radiolucency doubled at 4 years. Cox regression analysis revealed that the preoperative radiolucency size was a risk factor for persistent periapical radiolucency. CONCLUSIONS: The efficacy of root canal treatment for apical periodontitis was predictable. When the radiolucency changed by 20 % or more in volume on CBCT scans at 1 year after treatment, reversal of the radiographic healing tendency was rare. CLINICAL SIGNIFICANCE: The volumetric changes in radiolucency on CBCT could reflect trends in the healing process and may foster early clinical decision-making.

Capillarity Constructed Open Siphon for Sustainable Drainage.

Siphon is an effective method to transfer liquid from a higher to a lower level, which has many applications in hygienic design, clinical apparatus, and hydraulic engineering. Traditional operation requires energy to overcome gravity and establish flow in a closed system. Achieving sustainable high flux siphon drainage without energy input remains a challenge due to viscous dissipation. Here, an unexpected open siphon behavior on the South American pitcher plant Heliamphora minor consisting of trichomes covered pitcher and a wedge-shaped sheath is examined. Exploiting the concept of Digital Twin, a new biomimetic research method by transforming the biological sample to a virtual 3D model is proposed and unveiled that maintained connection of wicking on sub-millimeter long trichomes due to asymmetric pressure distribution and ascending in wedge sheath under unbalanced pressure forms continuous surface flow. Exploring this mechanism, a biomimetic siphon device achieving continuous high flux exposed to ambient air is constructed. Besides, particles floating on the meniscus in the outside wedge move under a curvature gradient as water ascends, which implies a biological nutrient capture method and new dust collection manner in the drainage system. Applying the underlying principle enhances the siphon efficiency of floor drains and has the potential for other liquid transfer device design improvements.

Exploiting Sound for Emerging Applications of Extracellular Vesicles.

Extracellular vesicles are nano- to microscale, membrane-bound particles released by cells into extracellular space, and act as carriers of biomarkers and therapeutics, holding promising potential in translational medicine. However, the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease treatment. Here, we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic nanovesicles. We first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle technologies. We discuss the acoustic-assisted diagnostic methods including the purification, manipulation, biosensing, and bioimaging of extracellular vesicles. Then, we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic nanovesicles. Finally, we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.

Mammalian IRE1α dynamically and functionally coalesces with stress granules.

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity.

Effectiveness of physiotherapeutic scoliosis-specific exercises on three-dimensional spinal deformities in patients with adolescent idiopathic scoliosis: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of physiotherapeutic scoliosis-specific exercises (PSSE) on coronal, horizontal, and sagittal deformities of the spine in adolescent idiopathic scoliosis (AIS) as well as how curve severity, intervention duration, and intervention type could modify these effects. DATA SOURCES: Data sources included the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases, searched from their inception to September 5, 2023. STUDY SELECTION: Clinical controlled trials reporting the effects of PSSE on the Cobb angle, angle of trunk rotation (ATR), thoracic kyphosis (TK), or lumbar lordosis (LL) in AIS patients aged 10 to 18 years. The experimental groups received PSSE; the control groups received standard care (observation or bracing) or conventional exercise such as core stabilization exercise, pilates, PNF, and other non-specific exercise. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The quality of the studies was assessed using the Cochrane Handbook version 5.1.0 risk of bias assessment and the JBI Center for Evidence-Based Health Care (2016) of quasi-experimental research authenticity assessment tool. The level and certainty of evidence was rated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The protocol for this study was registered in PROSPERO (CRD42023404996). DATA SYNTHESIS: Twelve randomized controlled trials (RCTs) and five non-RCTs (NRCTs) were meta-analyzed separately. The results indicated that compared with other non-surgical management, PSSE significantly improved the Cobb angle, ATR, and TK, whereas the LL improvement was not statistically significant. Additionally, the efficacy of PSSE on Cobb angle was not significant in patients with curve severity ≥30° compared with controls. Nevertheless, the pooled effect of PSSE on Cobb angle was not significantly modified by intervention duration and intervention type, and on ATR was not significantly modified by intervention duration. The overall quality of evidence according to GRADE was moderate to low for RCT and very low for NRCT. CONCLUSIONS: PSSE exhibited positive benefits on the Cobb angle, ATR, and TK in patients with AIS compared to other non-surgical therapies. In addition, the effectiveness of PSSE may be independent of intervention duration and intervention type, but may be influenced by the initial Cobb angle. However, more RCTs are needed in the future to validate the efficacy of PSSE in moderate AIS with a mean Cobb ≥30°. Current evidence is limited by inconsistent control group interventions and small sample size of the studies.

Ultrathin Boundary-Less SnO2 Films with Surface-Activated Two-Dimensional Nanograins Enable Fast and Sensitive Hydrogen Gas Sensing.

Fast and reliable semiconductor hydrogen sensors are crucially important for the large-scale utilization of hydrogen energy. One major challenge that hinders their practical application is the elevated temperature required, arising from undesirable surface passivation and grain-boundary-dominated electron transportation in the conventional nanocrystalline sensing layers. To address this long-standing issue, in the present work, we report a class of highly reactive and boundary-less ultrathin SnO2 films, which are fabricated by the topochemical transformation of 2D SnO transferred from liquid Sn-Bi droplets. The ultrathin SnO2 films are purposely made to consist of well-crystallized quasi-2D nanograins with in-plane grain sizes going beyond 30 nm, whereby the hydroxyl adsorption and grain boundary side-effects are effectively suppressed, giving rise to an activated (101)-dominating dangling-bond surface and a surface-controlled electrical transportation with an exceptional electron mobility of 209 cm2 V-1 s-1. Our work provides a new cost-effective strategy to disruptively improve the gas reception and transduction of SnO2. The proposed chemiresistive sensors exhibit fast, sensitive, and selective hydrogen sensing performance at a much-reduced working temperature of 60 °C. The remarkable sensing performance as well as the simple and scalable fabrication process of the ultrathin SnO2 films render the thus-developed sensors attractive for long awaited practical applications in hydrogen-related industries.

Does "National Civilized City" policy mitigate air pollution in China? A spatial Durbin difference-in-differences analysis.

"National Civilized City" (NCC) is regarded as China's highest honorary title and most valuable city brand. To win and maintain the "golden city" title, municipal governments must pay close attention to various key appraisal indicators, mainly environmental ones. In this study we verify whether cities with the title are more likely to mitigate SO2 pollution. We adopt the spatial Durbin difference-in-differences (DID) model and use panel data of 283 Chinese cities from 2003 to 2018 to analyze the local (direct) and spillover effects (indirect) of the NCC policy on SO2 pollution. We find that SO2 pollution in Chinese cities is not randomly distributed in geography, suggesting the existence of spatial spillovers and possible biased estimates. Our study treats the NCC policy as a quasi-experiment and incorporates spatial spillovers of NCC policy into a classical DID model to verify this assumption. Our findings show: (1) The spatial distribution of SO2 pollution represents strong spatial spillovers, with the most highly polluted regions mainly situated in the North China Plain. (2) The Moran's I test results confirms significant spatial autocorrelation. (3) Results of the spatial Durbin DID models reveal that the civilized cities have indeed significantly mitigated SO2 pollution, indicating that cities with the honorary title are acutely aware of the environment in their bid to maintain the golden city brand. As importantly, we notice that the spatial DID term is also significant and negative, implying that neighboring civilized cities have also mitigated their own SO2 pollution. Due to demonstration and competition effects, neighboring cities that won the title ostensibly motivates local officials to adopt stringent policies and measures for lowering SO2 pollution and protecting the environment in competition for the golden title. The spatial autoregressive coefficient was significant and positive, indicating that SO2 pollution of local cities has been deeply affected by neighbors. A series of robustness check tests also confirms our conclusions. Policy recommendations based on the findings for protecting the environment and promoting sustainable development are proposed.

Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria.

Messenger RNA (mRNA) therapeutics delivered via lipid nanoparticles hold the potential to treat metabolic diseases caused by protein deficiency, including propionic acidemia (PA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Herein we report results from multiple independent preclinical studies of mRNA-3927 (an investigational treatment for PA), mRNA-3705 (an investigational treatment for MMA), and mRNA-3210 (an investigational treatment for PKU) in murine models of each disease. All 3 mRNA therapeutics exhibited pharmacokinetic/pharmacodynamic (PK/PD) responses in their respective murine model by driving mRNA, protein, and/or protein activity responses, as well as by decreasing levels of the relevant biomarker(s) when compared to control-treated animals. These preclinical data were then used to develop translational PK/PD models, which were scaled allometrically to humans to predict starting doses for first-in-human clinical studies for each disease. The predicted first-in-human doses for mRNA-3927, mRNA-3705, and mRNA-3210 were determined to be 0.3, 0.1, and 0.4 mg/kg, respectively.

Vibration-Dependent Dual-Phosphorescent Cu4 Nanocluster with Remarkable Piezochromic Behavior.

The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C-p-NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher-energy emission peak of Cu4 gradually disappeared, leaving the lower-energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle-dispersive synchrotron X-ray diffraction results revealed that the reduced inter-cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C-H···N and N-H···N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands´ vibration, resulting in the vanishing of the higher-energy peak. In situ high-pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4.

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Design: Retrospective cohort study. Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Background: Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. Methods: A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Results: Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Conclusion: Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

LTBP2 regulates cisplatin resistance in GC cells via activation of the NF-κB2/BCL3 pathway.

Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor ß-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2's impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients.

Effects of tacrolimus on proteinuria in Chinese and Indian patients with idiopathic membranous nephropathy: the results of machine learning study.

PURPOSE: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. METHODS: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml. RESULTS: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. CONCLUSION: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.