Virally delivered CMYA5 enhances the assembly of cardiac dyads.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) lack nanoscale structures essential for efficient excitation-contraction coupling. Such nanostructures, known as dyads, are frequently disrupted in heart failure. Here we show that the reduced expression of cardiomyopathy-associated 5 (CMYA5), a master protein that establishes dyads, contributes to dyad disorganization in heart failure and to impaired dyad assembly in hiPSC-CMs, and that a miniaturized form of CMYA5 suitable for delivery via an adeno-associated virus substantially improved dyad architecture and normalized cardiac function under pressure overload. In hiPSC-CMs, the miniaturized form of CMYA5 increased contractile forces, improved Ca2+ handling and enhanced the alignment of sarcomere Z-lines with ryanodine receptor 2, a protein that mediates the sarcoplasmic release of stored Ca2+. Our findings clarify the mechanisms responsible for impaired dyad structure in diseased cardiomyocytes, and suggest strategies for promoting dyad assembly and stability in heart disease and during the derivation of hiPSC-CMs.

An ensemble machine learning model to uncover potential sites of hazardous waste illegal dumping based on limited supervision experience.

With the soaring generation of hazardous waste (HW) during industrialization and urbanization, HW illegal dumping continues to be an intractable global issue. Particularly in developing regions with lax regulations, it has become a major source of soil and groundwater contamination. One dominant challenge for HW illegal dumping supervision is the invisibility of dumping sites, which makes HW illegal dumping difficult to be found, thereby causing a long-term adverse impact on the environment. How to utilize the limited historic supervision records to screen the potential dumping sites in the whole region is a key challenge to be addressed. In this study, a novel machine learning model based on the positive-unlabeled (PU) learning algorithm was proposed to resolve this problem through the ensemble method which could iteratively mine the features of limited historic cases. Validation of the random forest-based PU model showed that the predicted top 30% of high-risk areas could cover 68.1% of newly reported cases in the studied region, indicating the reliability of the model prediction. This novel framework will also be promising in other environmental management scenarios to deal with numerous unknown samples based on limited prior experience.

Data-driven approaches linking wastewater and source estimation hazardous waste for environmental management.

Industrial enterprises are major sources of contaminants, making their regulation vital for sustainable development. Tracking contaminant generation at the firm-level is challenging due to enterprise heterogeneity and the lack of a universal estimation method. This study addresses the issue by focusing on hazardous waste (HW), which is difficult to monitor automatically. We developed a data-driven methodology to predict HW generation using wastewater big data which is grounded in the availability of this data with widespread application of automatic sensors and the logical assumption that a correlation exists between wastewater and HW generation. We created a generic framework that used representative variables from diverse sectors, exploited a data-balance algorithm to address long-tail data distribution, and incorporated causal discovery to screen features and improve computation efficiency. Our method was tested on 1024 enterprises across 10 sectors in Jiangsu, China, demonstrating high fidelity (R² = 0.87) in predicting HW generation with 4,260,593 daily wastewater data.

Powdery mildew effectors AVRA1 and BEC1016 target the ER J-domain protein HvERdj3B required for immunity in barley.

The barley powdery mildew fungus, Blumeria hordei (Bh), secretes hundreds of candidate secreted effector proteins (CSEPs) to facilitate pathogen infection and colonization. One of these, CSEP0008, is directly recognized by the barley nucleotide-binding leucine-rich-repeat (NLR) receptor MLA1 and therefore is designated AVRA1. Here, we show that AVRA1 and the sequence-unrelated Bh effector BEC1016 (CSEP0491) suppress immunity in barley. We used yeast two-hybrid next-generation interaction screens (Y2H-NGIS), followed by binary Y2H and in planta protein-protein interactions studies, and identified a common barley target of AVRA1 and BEC1016, the endoplasmic reticulum (ER)-localized J-domain protein HvERdj3B. Silencing of this ER quality control (ERQC) protein increased Bh penetration. HvERdj3B is ER luminal, and we showed using split GFP that AVRA1 and BEC1016 translocate into the ER signal peptide-independently. Overexpression of the two effectors impeded trafficking of a vacuolar marker through the ER; silencing of HvERdj3B also exhibited this same cellular phenotype, coinciding with the effectors targeting this ERQC component. Together, these results suggest that the barley innate immunity, preventing Bh entry into epidermal cells, requires ERQC. Here, the J-domain protein HvERdj3B appears to be essential and can be regulated by AVRA1 and BEC1016. Plant disease resistance often occurs upon direct or indirect recognition of pathogen effectors by host NLR receptors. Previous work has shown that AVRA1 is directly recognized in the cytosol by the immune receptor MLA1. We speculate that the AVRA1 J-domain target being inside the ER, where it is inapproachable by NLRs, has forced the plant to evolve this challenging direct recognition.

Evaluating the psychometric properties of the simplified Chinese version of PROMIS-29 version 2.1 in patients with hematologic malignancies.

The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients' perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach's α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P < 0.001). Confirmatory factor analysis (CFA) indicated a good model fit, with indices of χ2/df (2.602), IFI (0.960), and RMSEA (0.067). The Average Variance Extracted (AVE) values for the seven dimensions of PROMIS-29 V2.1, ranging from 0.500 to 0.910, demonstrated satisfactory convergent validity. Discriminant validity was confirmed by ideal √AVE values. The Chinese version of the PROMIS-29 V2.1 profile has been validated as an effective instrument for assessing symptoms and functions in patients with hematological malignancy, underscoring its reliability and applicability in this specific patient group.

Structural Pharmacology of TRPV4 Antagonists.

The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small-molecule antagonists, which may facilitate future drug discovery targeting TRPV4.

Electrochemical E-Selective Semireductive Dicarboxylation of Aryl Alkynes with CO2.

Herein, we report an electrochemical protocol for the dicarboxylation of aryl alkynes using CO2. With a graphite rod as the cathode and Al as the sacrificial anode, a series of valuable butenedioic acids are obtained in moderate to excellent yields with an E/Z ratio up to 50:1. This method features high E-selectivity, high step and atom economy, easy scalability, and a nice substrate scope, which renders it appealing for promising applications in organic synthesis and materials chemistry.

Effects of combined microplastics and heavy metals pollution on terrestrial plants and rhizosphere environment: A review.

Microplastics (MPs) can enter the soil environment through industry, agricultural production and daily life sources. Their interaction with heavy metals (HMs) poses a significant threat to a variety of terrestrial ecosystems, including agricultural ones, thereby affecting crop quality and threatening human health. This review initially addresses the impact of single and combined contamination with MPs and HMs on soil environment, including changes in soil physicochemical properties, microbial community structure and diversity, fertility, enzyme activity and resistance genes, as well as alterations in heavy metal speciation. The article further explores the effects of this pollution on the growth characteristics of terrestrial plants, such as plant biomass, antioxidant systems, metabolites and photosynthesis. In general, the combined contaminants tend to significantly affect soil environment and terrestrial plant growth, i.e., the impact of combined contaminants on plants weight ranged from -87.5% to 4.55%. Similarities and differences in contamination impact levels stem from the variations in contaminant types, sizes and doses of contaminants and the specific plant growth environments. In addition, MPs can not only infiltrate plants directly, but also significantly affect the accumulation of HMs in terrestrial plants. The heavy metals concentration in plants under the treatment of MPs were 70.26%-36.80%. The co-occurrence of these two pollution types can pose a serious threat to crop productivity and safety. Finally, this study proposes suggestions for future research aiming to address current gaps in knowledge, raises awareness about the impact of combined MPs + HMs pollution on plant growth and eco-environmental security.

Mononuclear Iron Pyridinethiolate Complex Promoted CO2 Photoreduction via Rapid Intramolecular Electron Transfer.

Designing earth-abundant metal complexes as efficient molecular photocatalysts for visible light-driven CO2 reduction is a key challenge in artificial photosynthesis. Here, we demonstrated the first example of a mononuclear iron pyridine-thiolate complex that functions both as a photosensitizer and catalyst for CO2 reduction. This single-component bifunctional molecular photocatalyst efficiently reduced CO2 to formate and CO with a total turnover number (TON) of 46 and turnover frequency (TOF) of 11.5 h-1 in 4 h under visible light irradiation. Notably, the quantum yield was determined to be 8.4 % for the generation of formate and CO at 400 nm. Quenching experiments indicate that high photocatalytic activity is mainly attributed to the rapid intramolecular quenching protocol. The mechanism investigation by DFT calculation and electrochemical studies revealed that the protonation of Febpy(pyS)2 is indispensable step for photocatalytic CO2 reduction.

Freezing Shrinkage Dynamics and Surface Dendritic Growth of Floating Refractory Alloy Droplets in Outer Space.

The freezing shrinkage and dendritic growth are of great importance for various alloys solidified from high-temperature liquids to solids since they dominate microstructure patterns and follow-up processing. However, the microgravity freezing shrinkage dynamics is scarcely explored on the ground as it is hard to suppress the strong natural convection inside liquid alloys. Here, a series of in-orbit solidification experiments is conducted aboard the China Space Station with a long-term stable 10-5 g0 microgravity condition. The highest temperature up to 2265 K together with substantial liquid undercoolings far from a thermodynamically stable state are attained for both Nb82.7Si17.3 and Zr64V36 refractory alloys. Furthermore, the solidification under microgravity of a droplet is simulated to reveal the liquid-solid interface migration, temperature gradient, and flow field. The microgravity solidification process leads to freezing shrinkage cavities and distinctive surface dendritic microstructure patterns. The combined effects of shrinkage dynamics and liquid surface flow in outer space result in the dendrites growing not only along the tangential direction but also along the normal direction to the droplet surface. These space experimental results contribute to a further understanding of the solidification behavior of liquid alloys under a weaker convection condition, which is often masked by gravity on the ground.

Metastable Liquid Properties and Surface Flow Patterns of Ultrahigh Temperature Alloys Explored in Outer Space.

The metastable liquid properties and chemical bonds beyond 2000 K remain a huge challenge for ground-based research on liquid materials chemistry. We show the strong undercooling capability, metastable liquid properties and surface wave patterns of refractory Nb-Si and Zr-V binary alloys explored in space environment. The floating droplet of Nb82.7Si17.3 eutectic alloy superheated up to 2338 K exhibited an extreme undercooling of 437 K, approaching the 0.2TE threshold for homogeneous nucleation of liquid-solid reaction. The microgravity state endowed alloy droplets with nearly perfect sphericity and thus ensured the high accuracy to determine metastable undercooled liquid properties. A special kind of swirling flow was induced for liquid alloy owing to Marangoni convection, which resulted in the spiral microstructures on Zr64V36 alloy surface during liquid-solid phase transition. The coupled impacts of surface nucleation and surface flow brought in a novel olivary shape for these binary alloys. Furthermore, the chemical bonds and atomic structures of high temperature liquids were revealed to understand the liquid properties in outer space circumstances.

Allosteric Activation of α7 Nicotinic Acetylcholine Receptors by Novel 2-Arylamino-thiazole-5-carboxylic Acid Amide Derivatives for the Improvement of Cognitive Deficits in Mice.

Enhancing α7 nAChR function serves as a therapeutic strategy for cognitive disorders. Here, we report the synthesis and evaluation of 2-arylamino-thiazole-5-carboxylic acid amide derivatives 6-9 that as positive allosteric modulators (PAMs) activate human α7 nAChR current expressed in Xenopus ooctyes. Among the 4-amino derivatives, a representative atypical type I PAM 6p exhibits potent activation of α7 current with an EC50 of 1.3 µM and the maximum activation effect on the current over 48-fold in the presence of acetylcholine (100 µM). The structure-activity relationship (SAR) analysis reveals that the 4-amino group is crucial for the allosteric activation of α7 currents by compound 6p as the substitution of 4-methyl group results in its conversion to compound 7b (EC50 = 2.1 µM; max effect: 58-fold) characterized as a typical type I PAM. Furthermore, both 6p and 7b are able to rescue auditory gating deficits in mouse schizophrenia-like model of acoustic startle prepulse inhibition.

Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex.

BACKGROUND: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear. METHODS: Given the known role of Ptpn23 (protein tyrosine phosphatase, nonreceptor type 23) in regulating membrane deformation, its expression in patients with dilated cardiomyopathy was determined. Taking advantage of Cre/Loxp, CRISPR/Cas9, and adeno-associated virus 9 (AAV9)-mediated in vivo gene editing, we generated cardiomyocyte-specific Ptpn23 and Actn2 (α-actinin-2, a major component of Z-discs) knockout mice. We also perturbed the DGC by using dystrophin global knockout mice (DmdE4*). MM 4-64 and Di-8-ANEPPS staining, Cav3 immunofluorescence, and transmission electron microscopy were performed to determine T-tubule structure in isolated cells and intact hearts. In addition, the assembly of the DGC with Ptpn23 and dystrophin loss of function was determined by glycerol-gradient fractionation and SDS-PAGE analysis. RESULTS: The expression level of Ptpn23 was reduced in failing hearts from dilated cardiomyopathy patients and mice. Genetic deletion of Ptpn23 resulted in disorganized T-tubules with enlarged diameters and progressive dilated cardiomyopathy without affecting sarcomere organization. AAV9-mediated mosaic somatic mutagenesis further indicated a cell-autonomous role of Ptpn23 in regulating T-tubule formation. Genetic and biochemical analyses showed that Ptpn23 was essential for the integrity of costameres, which anchor the T-tubule membrane to Z-discs, through interactions with α-actinin and dystrophin. Deletion of α-actinin altered the subcellular localization of Ptpn23 and DGCs. In addition, genetic inactivation of dystrophin caused similar T-tubule defects to Ptpn23 loss-of-function without affecting Ptpn23 localization at Z-discs. Last, inducible Ptpn23 knockout at 1 month of age showed Ptpn23 is also required for the maintenance of T-tubules in adult cardiomyocytes. CONCLUSIONS: Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.

Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.

AIM: The study aimed to use network pharmacology research and in vitro experiments to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary thyroid carcinoma. BACKGROUND: Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis are the leading causes of death in patients with PTC. A key research focus in thyroid cancer treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including cancer, but no study has been undertaken to determine whether it can help prevent PTC. OBJECTIVE: In this study, we attempted to determine through network pharmacology and in vitro experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle and invasive migration. METHODS: To predict the probable targets and underlying mechanisms of silybin against PTC, a network pharmacology research was performed. In vitro experiments were conducted to further evaluate silybin's anti-cancer properties and priority targets against PTC. RESULTS: The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment analysis suggested that the target genes were enriched in functions and pathways related to PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks, the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1), N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint gene expression levels were positively correlated with the expression levels of the hub genes. Silybin decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations. When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked, CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were dramatically reduced, while E-cadherin expression was significantly elevated. CONCLUSION: These findings provide preliminary evidence that silybin inhibits PTC cell proliferation, metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological checkpoint gene expression levels. These studies provide a theoretical and experimental scientific basis for the potential anticancer effects of silybin on PTC.

Molecular Engineering of Copper Phthalocyanine for CO2 Electroreduction to Methane.

Efficient electrochemical CO2 reduction reaction (ECO2RR) to multi-electron reductive products remains a great challenge. Herein, molecular engineering of copper phthalocyanines (CuPc) was explored by modifying electron-withdrawing groups (EWGs) (cyano, sulfonate anion) and electron-donating groups (EDGs) (methoxy, amino) to CuPc, then supporting onto carbon paper or carbon cloth by means of droplet coating, loading with carbon nanotubes and coating in polypyrrole (PPy). The results showed that the PPy-coated CuPc effectively catalysed ECO2RR to CH4. Interestingly, experimental results and DFT calculations indicated EWGs markedly improved the selectivity of methane for the reason that the introduction of EWGs reduces electron density of catalytic active center, resulting in a positive move to initial reduction potential. Otherwise, the modification of EDGs significantly reduces the selectivity towards methane. This electronic effect and heterogenization of CuPc are facile and effective molecular engineering, benefitting the preparation of electrocatalysts for further reduction of CO2.

[The role of mitochondria-associated endoplasmic reticulum membranes in age-related cardiovascular diseases].

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the physical connection sites between mitochondria and endoplasmic reticulum (ER). As the compartments controlling substance and information communications between ER and mitochondria, MAMs were involved in the regulation of various pathophysiological processes, such as calcium homeostasis, mitochondrial morphology and function, lipid metabolism and autophagy. In the past decades, accumulating lines of evidence have revealed the pivotal role of MAMs in diverse cardiovascular diseases (CVD). Aging is one of the major independent risk factors for CVD, which causes progressive degeneration of the cardiovascular system, leading to increased morbidity and mortality of CVD. This review aims to summarize the research progress of MAMs in age-related CVD, and explore new targets for its prevention and treatment.

Comparison of temporary external and percutaneous k-wire fixations for treatment of ankle fracture-dislocations.

PURPOSE: Ankle fracture-dislocations are among the most severe injuries, and the use of an external fixator as a recommended fixation method has some disadvantages. The aim of this study was to compare the clinical outcomes and complication rates of external and K-wire fixations in the treatment of ankle fracture dislocations. METHODS: A total of 67 patients with ankle fracture-dislocations requiring temporary external or percutaneous K-wire fixation were included. The exclusion criteria were pilon fractures, open fractures, and those who required acute open reduction internal fixation (ORIF). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, a 10-point visual analog scale (VAS) score (range 0-10), and complications before and after the definitive surgery were recorded. RESULTS: A significant difference between the two groups was not observed for age, sex, affected side, fracture type, smoking status, or diabetes. The average AOFAS scores were 83.2 and 83.3, the median VAS scores were 3 and 3, and the complication rates were 32.4% and 6.7% in the external and K-wire fixation groups, respectively (p = 0.010). However, skin necrosis, re-dislocation of the ankle, surgical wound infection, and posttraumatic ankle osteoarthritis frequency were not significantly different between the groups, except for pin-sites infection (p = 0.036). CONCLUSION: Ankle fracture-dislocations using percutaneous k-wire fixation showed a low rate of complications and favorable clinical outcomes. This method could be a good alternative treatment option for ankle fracture-dislocations.

5-aminolevulinic acid photodynamic therapy using 560-1200 nm followed by 420-1200 nm broadband light in the treatment of moderate-to-severe acne.

BACKGROUND: Moderate-to-severe acne vulgaris, which is a chronic inflammatory skin disease, seriously impacts millions of people. However, traditional therapies may cause severe adverse reactions that are unacceptable to many patients, thus limiting the further application of these therapies. Novel therapeutic approaches to effectively treat moderate-to-severe acne vulgaris with minimal adverse reactions are urgently needed. In this retrospective study, we investigated the efficacy and adverse reactions of photodynamic therapy (PDT) using 560-1200 nm followed by 420-1200 nm broadband light (BBL). METHODS: Twenty-four patients with moderate-to-severe acne vulgaris were included in the study and all patients expressed a strong desire for beauty. After aminolevulinic acid (ALA) gel applied, the entire face was sequentially irradiated by using BBL with a 560 nm cut-off filter (560-1200 nm), followed by BBL with a 420 nm cut-off filter (420-1200 nm). The clinical efficacy was evaluated by the proportion of patients achieving cured response and excellent response (effective rate), based on the percentage of lesions reduction (treatment rate). The fluorescent images and photographs of acne vulgaris were recorded. Pain and other common local adverse reactions during the treatment were also recorded and evaluated. RESULTS: In patients with moderate acne, the mean treatment rates were 57.74 ± 16.40 (%) and 87.40 ± 8.521 (%) at the 6th week and 12th week of treatment, respectively. In patients with severe acne, the mean treatment rates were 60.95 ± 12.06 (%) and 85.04 ± 9.115 (%) at the 6th week and 12th week of treatment, respectively. At the 6th and 12th weeks of treatment, the effective rates of patients were 20.00 % and 93.33 % in patients with moderate acne, and 0.000 % and 88.89 % in patients with severe acne, respectively. Pain scores were significantly higher in patients with severe acne compared to patients with moderate acne when receiving 560-1200 nm BBL-PDT. Additionally, patients when receiving 420-1200 nm BBL-PDT exhibited significantly higher pain scores than those when receiving 560-1200 nm BBL-PDT. The degree of erythema was more severe in patients with severe acne than in those with moderate acne. The pigmentation was observed in one patient with moderate acne and one patient with severe acne. CONCLUSION: The 560-1200 nm and 420-1200 nm BBL-PDT therapy can effectively treat moderate-to-severe acne vulgaris with tolerable adverse reactions, providing a new option for patients with higher esthetic requirements.

Nogo-B mediates endothelial oxidative stress and inflammation to promote coronary atherosclerosis in pressure-overloaded mouse hearts.

AIMS: Endothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE-/- mice with pressure overload. METHODS AND RESULTS: We generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE-/- background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE-/- mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE-/- mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1ß), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE-/- mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. CONCLUSION: Our study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE-/- mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.

Relationships among body weight, lipids and bone mass in elderly individuals with fractures: A case-control study.

BACKGROUND: The prevalence of osteoporosis and low bone mass is steadily rising each year. Low body weight is commonly linked to diminished bone mass and serves as a robust predictor of osteoporosis. Nonetheless, the connection between body mass index (BMI), bone mineral density, and lipid profiles among the elderly remains elusive. AIM: To examine the association between BMI and bone mass, explore the correlation between lipid profiles and bone mass, and delve into the interplay between lipid metabolism and bone health. METHODS: The study included 520 patients aged ≥ 65 years (178 men and 342 women). Age, sex, weight, and height were recorded. Femoral neck bone mineral density and T scores were determined using a dual-energy X-ray absorptiometry scanner. Blood calcium (Ca), phosphorus (P), albumin (ALB), alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured. Patients were classified by sex (male and female), age (65-79 years and ≥ 80 years), and T score (normal bone mineral density, osteopenia and osteoporosis). RESULTS: Age, sex, BMI, and ALP and TG levels were independent risk factors for osteoporosis. For the 65-79- and ≥ 80-year-old groups, females presented lower T scores than males. Ca, P, ALB, ALP, TC, HDL and LDL levels were significantly different between men and women in the 65-79-year-old group. In addition, BMI and TG levels were significantly decreased in osteoporotic patients compared with patients with normal bone mass. TC levels declined in 65- to 79-year-old male and female osteoporosis patients. In the group of women aged ≥ 80 years, osteoporotic patients showed significantly increased ALP levels. Furthermore, we found positive correlations between BMI and TG levels in the male and female patient groups. However, we found no significant differences in ALB, Ca, P, HDL and LDL levels in osteoporotic patients compared to patients with normal bone mass. CONCLUSION: Osteoporotic patients showed significantly decreased BMI and TG levels compared with those with normal bone mass. BMI showed positive correlations with TG levels in male and female patients. These results indicate correlations between BMI and bone mass and between lipid profiles and bone mass.