Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.

We assessed the mechanisms by which nonencapsulated heme, released in the plasma of mice after exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult male and female C57BL/6 mice to Cl2 (500 ppm for 30 min), returned them to room air, and injected them intramuscularly with either human hemopexin (hHPX; 5 µg/g BW in 50-µL saline) or vehicle at 1 h post-exposure. Upon return to room air, Cl2-exposed mice, injected with vehicle, developed respiratory acidosis, increased concentrations of plasma proteins in the alveolar space, lung mitochondrial DNA injury, increased levels of free plasma heme, and major alterations of their lung proteome. hHPX injection mice mitigated the onset and development of lung and mitochondrial injury and the increase of plasma heme, reversed the Cl2-induced changes in 83 of 237 proteins in the lung proteome at 24 h post-exposure, and improved survival at 15 days post-exposure. Systems biology analysis of the lung global proteomics data showed that hHPX reversed changes in a number of key pathways including elF2 signaling, verified by Western blotting measurements. Recombinant human hemopexin, generated in tobacco plants, injected at 1 h post-Cl2 exposure, was equally effective in reversing acute lung and mtDNA injury. The results of this study offer new insights as to the mechanisms by which exposure to Cl2 results in acute lung injury and the therapeutic effects of hemopexin.NEW & NOTEWORTHY Herein, we demonstrate that exposure of mice to chlorine gas causes significant changes in the lung proteome 24 h post-exposure. Systems biology analysis of the proteomic data is consistent with damage to mitochondria and activation of eIF2, the master regulator of transcription and protein translation. Post-exposure injection of hemopexin, which scavenges free heme, attenuated mtDNA injury, eIF2α phosphorylation, decreased lung injury, and increased survival.

Elevating Lithium-Sulfur Battery Durability through Samarium Oxide/Ketjen Black Modified Separator.

Lithium-sulfur batteries have garnered significant attention as a promising next-generation battery technology due to their potential for high energy density. However, their practical application is hampered by slow reaction kinetics and the shuttle effect of lithium polysulfide intermediates. In this context, the authors introduce a pioneering solution in the form of a novel porous carbon nanostructure modified with samarium oxide, denoted as Sm2O3/KB. The material has a highly polar surface, allowing lithium polysulfide to be chemisorbed efficiently. The unsaturated sites provided by the oxygen vacancies of Sm2O3 promote Li2S nucleation, lowering the reaction energy barrier and accelerating Li2S dissolution. The porous structure of Ketjen Black provides a highly conductive channel for electron transport and effectively traps polysulfides. Meanwhile, the batteries with Sm2O3/KB/PP spacers exhibited remarkable electrochemical performances, including a low-capacity decay rate of only 0.046 % for 1000 cycles at 2 C and an excellent multiplicative performance of 624 mAh g-1 at 3 C. This work opens up a new avenue for the potential use of rare-earth-based materials in lithium-sulfur batteries.

Well-Defined Oligo(azobenzene-graft-mannose): Photostimuli Supramolecular Self-Assembly and Immune Effect Regulation.

The immune system can recognize and respond to pathogens of various shapes. Synthetic materials that can change their shape have the potential to be used in vaccines and immune regulation. The ability of supramolecular assemblies to undergo reversible transformations in response to environmental stimuli allows for dynamic changes in their shapes and functionalities. A meticulously designed oligo(azobenzene-graft-mannose) was synthesized using a stepwise iterative method and "click" chemistry. This involved integrating hydrophobic and photoresponsive azobenzene units with hydrophilic and bioactive mannose units. The resulting oligomer, with its precise structure, displayed versatile assembly morphologies and chiralities that were responsive to light. These varying assembly morphologies demonstrated distinct capabilities in terms of inhibiting the proliferation of cancer cells and stimulating the maturation of dendritic cells. These discoveries contribute to the theoretical comprehension and advancement of photoswitchable bioactive materials.

Solvent-free synthesis of defective Zr-based metal-organic framework from waste plastic bottles for highly efficient lomefloxacin removal.

Large amount of polyethylene terephthalate (PET) plastics waster and emerging contaminants in water, including fluoroquinolone antibiotics, pose challenges to human survival. In this work, a green synthesis scheme is proposed in which the defective UiO-66 (d-UiO-66) is fabricated via a solvent-free routine by using PET plastics waster as raw materials for lomefloxacin (LOM) removal. In comparison with defect-free UiO-66, the created defect imparts d-UiO-66 with higher porosity and abundant defective Zr sites, which are beneficial to boost LOM adsorption. As expected, d-UiO-66 exhibited excellent LOM adsorption performances, showcasing a saturation adsorption capacity of 588 mg g-1 and a kinetic rate constant of 0.204 g mg-1 h-1, which are 3.5 and 2.0 times higher than those of the pristine UiO-66, respectively. Remarkably, the LOM saturation adsorption capacity of d-UiO-66 surpasses that of all reported adsorbents. Mechanism study reveals that this outstanding adsorption performance of d-UiO-66 is mainly ascribed to the abundant defective sites, high porosity, together with the strong hydrogen bonding interaction and π-π stacking interaction between d-UiO-66 and LOM. Therefore, the d-UiO-66 obtained by the solvent-free method can not only effectively upcycle PET plastic waster, but also efficiently remove LOM, demonstrating a potential routine to simultaneous address the solid PET waster and wastewater.

Targeting STAT6 to mitigate sepsis-induced muscle atrophy and weakness: Modulation of mitochondrial dysfunction, ferroptosis, and CHI3L1-Mediated satellite cell loss.

Sepsis-induced muscle weakness is a debilitating consequence of prolonged critical illness, often associated with a poor prognosis. While recent research has shown that STAT6 functions as an inhibitor of myogenesis, its role in sepsis-induced muscle weakness remains unclear. In this study, we hypothesized that inhibiting STAT6 could attenuate sepsis-induced muscle atrophy and weakness, and we explored the underlying mechanisms. Leveraging a microarray dataset from sepsis patients, we identified significant enrichment of genes related to muscle function, ferroptosis, and the p53 signalling pathway in muscle tissue from sepsis patients. Using a murine sepsis model induced by cecum ligation and puncture (CLP), we explore the multifaceted role of STAT6 inhibition. Our findings demonstrate that STAT6 inhibition effectively attenuates muscle atrophy, enhances grip strength, preserves mitochondrial integrity, and modulates ferroptosis in septic mice. Additionally, we identify elevated levels of CHI3L1 in septic muscle tissue, which are significantly reduced by STAT6 inhibition. In-depth analysis of primary muscle satellite cells reveals that CHI3L1 overexpression is associated with increased expression of key regulators of satellite cell myogenicity, while negatively impacting cell viability. Silencing CHI3L1 expression mitigates satellite cell injury and loss, highlighting its pivotal role in sepsis-induced muscle damage. In summary, this study unveils the potential of STAT6 as a therapeutic target for mitigating sepsis-induced muscle atrophy and weakness. Our findings underscore the regulation of mitochondrial dysfunction, ferroptosis, and CHI3L1-mediated satellite cell damage by STAT6, offering promising avenues for therapeutic intervention in the management of sepsis-induced muscle weakness.

Depression promotes breast cancer progression by regulating amino acid neurotransmitter metabolism and gut microbial disturbance.

INTRODUCTION: Breast cancer (BC) is the most prevalent type of cancer and has the highest mortality among women worldwide. BC patients have a high risk of depression, which has been recognized as an independent factor in the progression of BC. However, the potential mechanism has not been clearly demonstrated. METHODS: To explore the correlation and mechanism between depression and BC progression, we induced depression and tumor in BC mouse models. Depression was induced via chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS). Amino acid (AA) neurotransmitter-targeted metabonomics and gut microbiota 16S rDNA gene sequencing were employed in the mouse model after evaluation with behavioral tests and pathological analysis. RESULTS: The tumors in cancer-depression (CD) mice grew faster than those in cancer (CA) mice, and lung metastasis was observed in CD mice. Metabonomics revealed that the neurotransmitters and plasma AAs in CD mice were dysregulated, namely the tyrosine and tryptophan pathways and monoamine neurotransmitters in the brain. Gut microbiota analysis displayed an increased ratio of Firmicutes/Bacteroides. In detail, the abundance of f_Lachnospiraceae and s_Lachnospiraceae increased, whereas the abundance of o_Bacteroidales and s_Bacteroides_caecimuris decreased. Moreover, the gut microbiota was more closely associated with AA neurotransmitters than with plasma AA. CONCLUSION: Depression promoted the progression of BC by modulating the abundance of s_Lachnospiraceae and s_Bacteroides_caecimuris, which affected the metabolism of monoamine neurotransmitters in the brain and AA in the blood.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma: A case report.

BACKGROUND: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases. CASE SUMMARY: A 64-year-old patient presented with dysphagia, without obvious cause. A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results. After multi-disciplinary consultations, combination chemotherapy (a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14) and esophageal cancer radiotherapy were initiated. Based on the results of genetic testing, we switched to a regimen of leucovorin + fluorouracil + oxaliplatin and cetuximab regimen for 8 cycles. Subsequently, capecitabine and bevacizumab were administered until the most recent follow-up, at which the tumor remained stable. CONCLUSION: Successful cetuximab chemotherapy treatment provides a reference for the non-operative and homogeneous treatment of different pathological types of synchronous MCPs.

HIV self-test performance evaluation among priority populations in rural Mozambique: Results from a community-based observational study.

BACKGROUND: In 2021, Mozambique initiated community-based oral HIV self-testing (HIVST) to increase testing access and uptake among priority groups, including adult males, adolescents, and young adults. Within an HIVST pilot project, we conducted a performance evaluation assessing participants' ability to successfully conduct HIVST procedures and interpret results. METHODS: A cross-sectional study was performed between February-March 2021 among employees, students (18-24 years of age), and community members, using convenience sampling, in two rural districts of Zambézia Province, Mozambique. We quantified how well untrained users performed procedures for the oral HIVST (Oraquick®) through direct observation using a structured checklist, from which we calculated an HIVST usability index (scores ranging 0-100%). Additionally, participants interpreted three previously processed anonymous HIVST results. False reactive and false non-reactive interpretation results were presented as proportions. Bivariate analysis was conducted using Chi-square and Fisher exact tests. RESULTS: A total of 312 persons participated (131[42%] community members, 71[23%] students, 110[35%] employees); 239 (77%) were male; the mean age was 28 years (standard deviation 10). Average usability index scores were 80% among employees, 86% among students, and 77% among community members. Main procedural errors observed included "incorrect tube positioning" (49%), "incorrect specimen collection" (43%), and "improper waiting time for result interpretation" (42%). From the presented anonymous HIVST results, 75% (n = 234) correctly interpreted all three results, while 9 (3%) of study participants failed to correctly interpret any results. Overall, 36 (12%) gave a false non-reactive result interpretation, 21 (7%) a false reactive result interpretation, and 14 (4%) gave both false non-reactive and false reactive result interpretations. Community members generally had lower performance. CONCLUSIONS: Despite some observed testing procedural errors, most users could successfully perform an HIVST. Educational sessions at strategic places (e.g., schools, workplaces), and support via social media and hotlines, may improve HIVST performance quality, reducing the risk of incorrect interpretation.

Effects of a Patient Portal Intervention to Address Diabetes Care Gaps: Protocol for a Pragmatic Randomized Controlled Trial.

BACKGROUND: Despite the potential to significantly reduce complications, many patients do not consistently receive diabetes preventive care. Our research team recently applied user-centered design sprint methodology to develop a patient portal intervention empowering patients to address selected diabetes care gaps (eg, no diabetes eye examination in last 12 months). OBJECTIVE: This study aims to evaluate the effect of our novel diabetes care gap intervention on completion of selected evidence-based diabetes preventive care services and secondary outcomes. METHODS: We are conducting a pragmatic randomized controlled trial of the effect of the intervention on diabetes care gaps. Adult patients with diabetes mellitus (DM) are recruited from primary care clinics affiliated with Vanderbilt University Medical Center. Participants are eligible if they have type 1 or 2 DM, can read in English, are aged 18-75 years, have a current patient portal account, and have reliable access to a mobile device with internet access. We exclude patients with medical conditions that prevent them from using a mobile device, severe difficulty seeing, pregnant women or women who plan to become pregnant during the study period, and patients on dialysis. Participants will be randomly assigned to the intervention or usual care. The primary outcome measure will be the number of diabetes care gaps among 4 DM preventive care services (diabetes eye examination, pneumococcal vaccination, hemoglobin A1c, and urine microalbumin) at 12 months after randomization. Secondary outcomes will include diabetes self-efficacy, confidence managing diabetes in general, understanding of diabetes preventive care, diabetes distress, patient portal satisfaction, and patient-initiated orders at baseline, 3 months, 6 months, and 12 months after randomization. An ordinal logistic regression model will be used to quantify the effect of the intervention on the number of diabetes care gaps at the 12-month follow-up. For dichotomous secondary outcomes, a logistic regression model will be used with random effects for the clinic and provider variables as needed. For continuous secondary outcomes, a regression model will be used. RESULTS: This study is ongoing. Recruitment was closed in February 2022; a total of 433 patients were randomized. Of those randomized, most (n=288, 66.5%) were non-Hispanic White, 33.5% (n=145) were racial or ethnic minorities, 33.9% (n=147) were aged 65 years or older, and 30.7% (n=133) indicated limited health literacy. CONCLUSIONS: The study directly tests the hypothesis that a patient portal intervention-alerting patients about selected diabetes care gaps, fostering understanding of their significance, and allowing patients to initiate care-will reduce diabetes care gaps compared with usual care. The insights gained from this study may have broad implications for developing future interventions to address various care gaps, such as gaps in cancer screening, and contribute to the development of effective, scalable, and sustainable approaches to engage patients in chronic disease management and prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04894903; https://classic.clinicaltrials.gov/ct2/show/NCT04894903. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56123.