Study of different pre-treatments in the comparison of the efficacy of photodynamic therapy for moderate to severe acne vulgaris.

OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment. METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week. RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88% for Group A, 62% for Group B, and 36% for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time. CONCLUSION: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

Dual-Site Bridging Mechanism for Bimetallic Electrochemical Oxygen Evolution.

Heterogeneous dual-site electrocatalysts are emerging cutting-edge materials for efficient electrochemical water splitting. However, the corresponding oxygen evolution reaction (OER) mechanism on these materials is still unclear. Herein, based on a series of in-situ spectroscopy experiments and density function theory (DFT) calculations, a new heterogeneous dual-site O-O bridging mechanism (DSBM) is proposed. This mechanism is to elucidate the sequential appearance of dual active sites through in-situ construction (hybrid ions undergo reconstruction initially), determine the crucial role of hybrid dual sites in this mechanism (with Ni sites preferentially adsorbing hydroxyls for catalysis followed by proton removal at Fe sites), assess the impact of O-O bond formation on the activation state of water (inducing orderliness of activated water), and investigate the universality (with Co doping in Ni(P4O11)). Under the guidance of this mechanism, with Fe-Ni(P4O11) as pre-catalyst, the in-situ formed Fe-Ni(OH)2 electrocatalyst has reached a record-low overpotential of 156.4 mV at current density of 18.0 mA cm-2. Successfully constructed Fe-Ni(P4O11)/Ti uplifting the overall efficacy of the phosphate from moderate to superior, positioning it as an innovative and highly proficient electrocatalyst for OER.

Effects of Social Support Provided by Disabled Older Adults to Others on Their Own Depressive Symptoms: A Moderated Mediation Model.

Purpose: While previous studies have extensively examined the impact of receiving positive social support during social support interactions on depressive symptoms among older adults, adverse effects experienced, such as being rejected or ignored, are often overlooked. Moreover, there has been limited discussion on the effects of giving social support to others. Thus, this study investigates the impacts of social support given by disabled older adults to others on their own depressive symptoms, as well as the mediating role of receiving social support (both positive and negative aspects) and the moderating effect of the activity of daily living (ADL). Patients and Methods: This cross-sectional, community-based study was conducted in Wenzhou and Jiaxing City, China, from September 2021 to September 2022, with a total of 255 disabled older adults meeting the inclusion and exclusion criteria. The data were collected face-to-face using a structured questionnaire. The participants were asked to complete the Barthel Index Scale, the Chinese version of the Positive and Negative Social Exchange Scale, the Giving Social Support questionnaire, and the Short Form Chinese Geriatric Depression Scale to measure disability, receiving positive and negative social support, giving social support, and depressive symptoms, respectively. Descriptive statistical analysis, correlation analysis, mediation effect tests, and moderation effect tests were used to analyse the questionnaire data. Results: The social support provided by disabled older adults to others primarily involved companionship and care. The positive aspect of social support received was largely emotional support, while the negative aspect was mainly characterised by failure to obtain help and unsympathetic behaviour. Providing social support was found to be associated with a potential beneficial effect on depressive symptoms, linked to lower severity, with this effect fully mediated by receiving social support. Specifically, receiving emotional support accounted for 56.63% of the effect size, while failure to obtain help and unsympathetic behaviour contributed 21.55%, and rejection and neglect collectively accounted for 21.83%. Additionally, the effect was partially moderated by ADL, with older adults exhibiting lower ADL scores showing a greater benefit from both giving and receiving social support compared to those with higher ADL scores. Conclusion: It is imperative to recognise and encourage disabled older adults to provide social support to others, especially emotional support, while reducing negative feedback, such as neglect and unnecessary blame. This could alleviate their depressive symptoms and promote psycho-social well-being.

CDYL loss promotes cervical cancer aggression by increasing PD-L1 expression via the suppression of IRF2BP2 transcription.

BACKGROUND: Recurrent or metastatic cervical cancer have an extremely low 5-year survival rates about 17% due to limited therapeutic options. CDYL plays a critical role in multiple cancer development, as an oncogene or tumor suppressor in a context-dependent manner. However, the role of CDYL in cervical carcinogenesis has not yet been explored. METHODS: CDYL expression was examined in cervical cancer and cell lines. The effect of CDYL/IRF2BP2/PD-L1 axis on malignant phenotypes of cervical cancer cells were tested with gain-of-function experiments. A mouse model of cervical cancer was developed to validate the in vitro results. RESULTS: Clinical data analysis revealed that CDYL was downregulated and associated with a poor prognosis in cervical cancer patients. CDYL overexpression suppressed cervical cancer cells proliferation and invasion in vitro and vivo assays and enhanced the immune response by decreasing PD-L1 expression and reversing the tumor immunosuppressing microenvironment. Mechanistically, CDYL inhibited the PD-L1 expression through transcriptionally suppressing IRF2BP2 in cervical cancer cells. CONCLUSIONS: Taken together, our findings established the crucial role of CDYL in cervical carcinogenesis and sensitivity for immune checkpoint blockade therapy, and supported the hypothesis that CDYL could be a potential novel immunotherapy response predictive biomarker for cervical cancer patients.

Elevated Glucose on Admission Was an Independent Risk Factor for 30-Day Major Adverse Cardiovascular Events in Patients with STEMI but Not NSTEMI.

Background: The purpose of this study was to evaluate the impact of glucose levels on admission, on the risk of 30-day major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI), and to assess the difference in outcome between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods: This study was a post hoc analysis of the Acute Coronary Syndrome Quality Improvement in Kerala Study, and 13,398 participants were included in the final analysis. Logistic regression models were used to assess the association between glucose levels on admission and the risk of 30-day MACEs, adjusting for potential confounders. Results: Participants were divided according to the glucose quintiles. There was a positive linear association between glucose levels at admission and the risk of 30-day MACEs in AMI patients [adjusted OR (95% CI): 1.05 (1.03, 1.07), p < 0.001]. Compared to participants with an admission glucose between 5.4 and 6.3 mmol/L, participants with the highest quintile of glucose level ( ≥ 10.7 mmol/L) were associated with increased risk of 30-day MACEs in the fully adjusted logistic regression model [adjusted OR (95% CI): 1.82 (1.33, 2.50), p < 0.001]. This trend was more significant in patients with STEMI (p for interaction = 0.036). Conclusions: In patients with AMI, elevated glucose on admission was associated with an increased risk of 30-day MACEs, but only in patients with STEMI.

Targeting the sulfur-containing amino acid pathway in leukemia.

sulfur-containing amino acids have been reported to patriciate in gene regulation, DNA methylation, protein synthesis and other physiological or pathological processes. In recent years, metabolism-related molecules of sulfur-containing amino acids affecting the occurrence, development and treatment of tumors have been implicated in various disorders, especially in leukemia. Here, we summarize current knowledge on the sulfur-containing amino acid metabolism pathway in leukemia and examine ongoing efforts to target this pathway, including treatment strategies targeting (a) sulfur-containing amino acids, (b) metabolites of sulfur-containing amino acids, and (c) enzymes and cofactors related to sulfur-containing amino acid metabolism in leukemia. Future leukemia therapy will likely involve innovative strategies targeting the sulfur-containing amino acid metabolism pathway.

Interaction characteristics and mechanism of Cr(VI)/Cr(III) with microplastics: Influence factor experiment and DFT calculation.

The coexistence of highly toxic heavy metal chromium and new pollutants microplastics has been widely present, and the interaction behavior and mechanism of the two are crucial for their environmental effects in coexisting environments, which urgently need to be further explored. Firstly, the interaction characteristics of polyamide (PA) and polyethylene (PE) with Cr(VI)/Cr(III) were investigated, where PA exhibited higher adsorption capacity of both Cr(VI) and Cr(III) than PE among various environmental conditions. The higher adsorption energy of PA on Cr(VI)/Cr(III) was also achieved by DFT calculation, and the bending configuration of PA during the adsorption process may be beneficial for its interaction with Cr. Then, the combination of characterization analysis and DFT calculation showed that significant chemical bonding occurred in the interaction between CO bond of PA and Cr(III), weak chemical interactions occurred in the adsorption of PE with Cr(III) and PA with Cr(VI), while the adsorption of PE with Cr(VI) was mainly physical effects. This study provides theoretical support for pollution control of microplastics and chromium in co-existing environment.

A novel inhalable nanobody targeting IL-4Rα for the treatment of asthma.

BACKGROUND: Inhalable biologics represent a promising approach to improve the efficacy and safety of asthma treatment. Although several mAbs targeting IL-4 receptor α chain (IL-4Rα) have been approved or are undergoing clinical trials, the development of inhalable mAbs targeting IL-4Rα presents significant challenges. OBJECTIVE: Capitalizing on the distinctive advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, we sought to develop a novel inhalable IL-4Rα Nb for effectively treating asthma. METHODS: Three IL-4Rα immunized Nb libraries were used to generate specific and functional IL-4Rα Nbs. LQ036, a bivalent Nb comprising 2 HuNb103 units, was constructed with a high affinity and specificity for human IL-4Rα. The efficacy, pharmacokinetics, and safety of inhaled LQ036 were evaluated in B-hIL4/hIL4RA humanized mice. RESULTS: LQ036 inhibited secreted embryonic alkaline phosphatase reporter activity, inhibited TF-1 cell proliferation, and suppressed phosphorylated signal transducer and activator of transduction 6 in T cells from patients with asthma. Crystal structure analysis revealed a binding region similar to dupilumab but with higher affinity, leading to better efficacy in blocking the signaling pathway. HuNb103 competed with IL-4 and IL-13 for IL-4Rα binding. Additionally, LQ036 significantly inhibited ovalbumin-specific IgE levels in serum, CCL17 levels in bronchoalveolar lavage fluid, bronchial mucous cell hyperplasia, and airway goblet cell hyperplasia in B-hIL4/hIL4RA humanized mice. Inhaled LQ036 exhibited favorable pharmacokinetics, safety, and tissue distribution, with higher concentrations observed in the lungs and bronchi. CONCLUSIONS: These findings from preclinical studies establish the safety and efficacy of inhaled LQ036, underscoring its potential as a pioneering inhalable biologic therapy for asthma.

Natural compound Alternol exerts a broad anti-cancer spectrum and a superior therapeutic safety index in vivo.

Introduction: Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms. Methods: We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity. Results: Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models. Conclusion: Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

Secondary Metabolites from Marine-Derived Fungus Penicillium rubens BTBU20213035.

Two new polyketide derivatives, penirubenones A and B (1 and 2), and two naturally rare amino-bis-tetrahydrofuran derivatives, penirubenamides A and B (3 and 4), together with nine known compounds (5-13) were isolated from the marine-derived fungus Penicillium rubens BTBU20213035. The structures were identified by HRESIMS and 1D and 2D NMR analyses, and their absolute configurations were determined by a comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy and 13C NMR data. We found that 6 exhibited antibacterial activity against Staphylococcus aureus, with an MIC value of 3.125 µg/mL, and 1 and 2 showed synergistic antifungal activity against Candida albicans at 12.5 and 50 µg/mL with 0.0625 µg/mL rapamycin.

A humanized trivalent Nectin-4-targeting nanobody drug conjugate displays potent antitumor activity in gastric cancer.

BACKGROUND: Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among cancer patients, coupled with a suboptimal postoperative survival prognosis. Nectin-4, an overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) to treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically for gastric cancer, and conventional immunoglobulin G (IgG)-based ADCs frequently encounter binding site barriers. Based on the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug conjugates (NDCs) for the treatment of gastric cancer. RESULTS: An immunized phage display library was established and employed for the selection of Nectin-4-specific Nbs using phage display technology. Subsequently, these Nbs were engineered into homodimers to enhance Nb affinity. To prolong in vivo half-life and reduce immunogenicity, we fused an Nb targeting human serum albumin (HSA), resulting in the development of trivalent humanized Nbs. Further, we site-specifically conjugated a monomethyl auristatin E (MMAE) at the C-terminus of the trivalent Nbs, creating Nectin-4 NDC (huNb26/Nb26-Nbh-MMAE) with a drug-to-antibody ratio (DAR) of 1. Nectin-4 NDC demonstrated excellent in vitro cell-binding activities and cytotoxic efficacy against cells with high Nectin-4 expression. Subsequent administration of Nectin-4 NDC to mice bearing NCI-N87 human gastric cancer xenografts demonstrated rapid tissue penetration and high tumor uptake through in vivo imaging. Moreover, Nectin-4 NDC exhibited noteworthy dose-dependent anti-tumor efficacy in in vivo studies. CONCLUSION: We have engineered a Nectin-4 NDC with elevated affinity and effective tumor uptake, further establishing its potential as a therapeutic agent for gastric cancer.

A novel approach for sludge deep-dewatering via flowing-out enhancement but not relying on cell lysis and bound water release.

Effective deep-dewatering is crucial for wastewater sludge management. Currently, the dominant methods focus on promoting cell lysis to release intracellular water, but these techniques often lead to secondary pollution and require stringent conditions, limiting their practical use. This study explores an innovative method using a commercially available complex quaternary ammonium salt surfactant, known as G-agent. This agent remarkably reduces the sludge water content from 98.6 % to 56.8 % with a low dosage (50 mg/g DS) and under neutral pH conditions. This approach surpasses Fenton oxidation in terms of dewatering efficiency and avoids the necessity for cell lysis and bound water release, thereby reducing the risk of secondary pollution in the filtrate, including heavy metals, nitrogen, phosphorus, and other contaminants. The G-agent plays a significant role in destabilizing flocs and enhancing flocculation during the conditioning and initial dewatering stages, effectively reducing the solid-liquid interfacial affinity of the sludge. In the compression filtration stage, the agent's solidification effect is crucial in forming a robust skeleton that improves pore connectivity within the filter cake, leading to increased water permeability, drainage performance and water flow-out efficiency. This facilitates deep dewatering of sludge without cell lysis. The study reveals that the G-agent primarily improves water flow-out efficiency rather than water flowability, indicating that cell lysis and bound water release are not indispensable prerequisites for sludge deep-dewatering. Furthermore, it presents an encouraging prospect for overcoming the limitations associated with conventional sludge deep-dewatering processes.

Advances in the application of traditional Chinese medicine during the COVID-19 recovery period: A review.

Since the emergence of the Coronavirus Disease 2019 (COVID-19) outbreak, significant advancements has been made in research, from limited knowledge about the disease to the development of a vaccine. Although the severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) appears to be decreasing and the threat of COVID-19 is waning, there have been widespread concerns about persistent symptoms or sequelae experienced by some patients even after recovering from COVID-19. Traditional Chinese medicine (TCM) has shown favorable treatment outcomes during the onset of COVID-19, and extensive studies have been carried out to explore the efficacy of TCM interventions during the COVID-19 recovery period. The purpose of this review is to comprehensively analyze these studies and provide new insights for the prevention and treatment of the post-COVID-19 condition.

A High-Throughput Screening of a Natural Products Library for Mitochondria Modulators.

Mitochondria, the energy hubs of the cell, are progressively becoming attractive targets in the search for potent therapeutics against neurodegenerative diseases. The pivotal role of mitochondrial dysfunction in the pathogenesis of various diseases, including Parkinson's disease (PD), underscores the urgency of discovering novel therapeutic strategies. Given the limitations associated with available treatments for mitochondrial dysfunction-associated diseases, the search for new potent alternatives has become imperative. In this report, we embarked on an extensive screening of 4224 fractions from 384 Australian marine organisms and plant samples to identify natural products with protective effects on mitochondria. Our initial screening using PD patient-sourced olfactory neurosphere-derived (hONS) cells with rotenone as a mitochondria stressor resulted in 108 promising fractions from 11 different biota. To further assess the potency and efficacy of these hits, the 11 biotas were subjected to a subsequent round of screening on human neuroblastoma (SH-SY5Y) cells, using 6-hydroxydopamine to induce mitochondrial stress, complemented by a mitochondrial membrane potential assay. This rigorous process yielded 35 active fractions from eight biotas. Advanced analysis using an orbit trap mass spectrophotometer facilitated the identification of the molecular constituents of the most active fraction from each of the eight biotas. This meticulous approach led to the discovery of 57 unique compounds, among which 12 were previously recognized for their mitoprotective effects. Our findings highlight the vast potential of natural products derived from Australian marine organisms and plants in the quest for innovative treatments targeting mitochondrial dysfunction in neurodegenerative diseases.

Development of a Health Behavioral Digital Intervention for Patients With Hypertension Based on an Intelligent Health Promotion System and WeChat: Randomized Controlled Trial.

BACKGROUND: The effectiveness of timely medication, physical activity (PA), a healthy diet, and blood pressure (BP) monitoring for promoting health outcomes and behavioral changes among patients with hypertension is supported by a substantial amount of literature, with "adherence" playing a pivotal role. Nevertheless, there is a lack of consistent evidence regarding whether digital interventions can improve adherence to healthy behaviors among individuals with hypertension. OBJECTIVE: The aim was to develop a health behavioral digital intervention for hypertensive patients (HBDIHP) based on an intelligent health promotion system and WeChat following the behavior change wheel (BCW) theory and digital micro-intervention care (DMIC) model and assess its efficacy in controlling BP and improving healthy behavior adherence. METHODS: A 2-arm, randomized trial design was used. We randomly assigned 68 individuals aged >60 years with hypertension in a 1:1 ratio to either the control or experimental group. The digital intervention was established through the following steps: (1) developing digital health education materials focused on adherence to exercise prescriptions, Dietary Approaches to Stop Hypertension (DASH), prescribed medication, and monitoring of BP; (2) using the BCW theory to select behavior change techniques; (3) constructing the intervention's logic following the guidelines of the DMIC model; (4) creating an intervention manual including the aforementioned elements. Prior to the experiment, participants underwent physical examinations at the community health service center's intelligent health cabin and received intelligent personalized health recommendations. The experimental group underwent a 12-week behavior intervention via WeChat, while the control group received routine health education and a self-management manual. The primary outcomes included BP and adherence indicators. Data analysis was performed using SPSS, with independent sample t tests, chi-square tests, paired t tests, and McNemar tests. A P value <.05 was considered statistically significant. RESULTS: The final analysis included 54 participants with a mean age of 67.24 (SD 4.19) years (n=23 experimental group, n=31 control group). The experimental group had improvements in systolic BP (-7.36 mm Hg, P=.002), exercise time (856.35 metabolic equivalent [MET]-min/week, P<.001), medication adherence (0.56, P=.001), BP monitoring frequency (P=.02), and learning performance (3.23, P<.001). Both groups experienced weight reduction (experimental: 1.2 kg, P=.002; control: 1.11 kg, P=.009) after the intervention. The diet types and quantities for both groups (P<.001) as well as the subendocardial viability ratio (0.16, P=.01) showed significant improvement. However, there were no statistically significant changes in other health outcomes. CONCLUSIONS: The observations suggest our program may have enhanced specific health outcomes and adherence to health behaviors in older adults with hypertension. However, a longer-term, larger-scale trial is necessary to validate the effectiveness. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062643; https://www.chictr.org.cn/showprojEN.html?proj=172782. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/46883.

Release characteristics and risk assessment of volatile sulfur compounds in municipal wastewater treatment plants.

In recent years, the malodorous gases generated by sewage treatment plants have gradually received widespread attention due to their sensory stimulation and health hazards. The emission concentration, sensory evaluation and health risk assessment of volatile sulfur compounds (VSCs) were all explored in two municipal wastewater treatment plants (WWTPs) with oxidation ditch and anaerobic/oxic treatment process, respectively. The VSCs concentration showed the highest amount in the primary treatment unit in both the two WWTPs (73.3% in Plant A and 93.0% in Plant B), while the H2S took the main role in the composition of VSCs. However, H2S took a larger percentage in Plant A (84.5% âˆ¼ 87.0%) rather than Plant B (61.2% âˆ¼ 83.5%), which may be due to the different operating conditions and sludge properties in different treatment process. Besides, H2S also gained the first rank in the sensory evaluation and health risk assessment, which may cause considerable sensory irritation and health risk to workers and surrounding residents. Furthermore, the influencing factor analyses of VSCs emission showed that the temperature of water and air, ORP of sludge made the greatest effect on VSCs release. This study provides theoretical and data support for the research of VSCs emission control in WWTPs.

Synthesis and Hypoglycemic Effect of Insulin from the Venom of Sea Anemone Exaiptasia diaphana.

Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five distinct ILPs in Exaiptasia diaphana, exhibiting varied sequences. Among these, ILP-Ap04 was successfully synthesized using solid phase peptide synthesis (SPPS) to evaluate its hypoglycemic activity. When tested in zebrafish, ILP-Ap04 significantly reduced blood glucose levels in a model of diabetes induced by streptozotocin (STZ) and glucose, concurrently affecting the normal locomotor behavior of zebrafish larvae. Furthermore, molecular docking studies revealed ILP-Ap04's unique interaction with the human insulin receptor, characterized by a detailed hydrogen-bonding network, which supports a unique mechanism for its hypoglycemic effects. Our findings suggest that sea anemones have evolved sophisticated strategies to activate insulin receptors in vertebrates, providing innovative insights into the design of novel drugs for the treatment of diabetes.