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Dye wastewater currently damages both human health and aquatic ecosystem, so to reduce its negative effects and promote sustainable development, this study optimizes cellulose extraction process from coconut coir pith via employing response surface methodology combined with Design Expert software (version 11.0.1.0, Copyright©2017, Stat-Ese Inc., USA). The recovered cellulose after alkalizing and decolorizing process is applied to assess its adsorption capability of methylene blue from water. Methylene blue adsorption capacity is evaluated based on operating factors: pH, contact time, methylene blue initial concentration and cellulose mass. The success of cellulose extraction process is established by Fourier-transform infrared spectroscopy, X-Ray Diffraction and Thermogravimetric analysis. The recovered cellulose particles have a high crystallinity index of 46.39% and high purity of 35.63% with an average diameter of 344 μm with a specific surface area of 3.303 m 2 .g −1 , a porous structure with a pore diameter of 34.952Å and pH pzc of 6.14. Under optimal adsorption conditions, methylene blue adsorption efficiency of 99.22% is achieved, and the process is favorable, reversible, and monolayer adsorption. The adsorption in this work is in good agreement with pseudo-second-order kinetic model and physical adsorption is the main adsorption mechanism. Importantly, the recovered cellulose has a significantly high adsorption capacity of 145.81 mg.g −1 after seven continuous using times. These findings propose that cellulose can recover from coconut coir pith by-product and holds a highly potential on dye removal from aqueous solution. Graphical abstract

Determining the best therapy for HIV-associated cryptococcal meningitis in resource-poor settings is controversial. In this trial in Vietnam, initial therapy with amphotericin B with flucytosine had better outcomes than amphotericin B alone or with fluconazole. There are approximately 1 million cases of cryptococcal meningitis annually and 625,000 deaths. 1 Treatment guidelines recommend induction therapy with amphotericin B deoxycholate (0.7 to 1 mg per kilogram of body weight per day) and flucytosine (100 mg per kilogram per day). 2 However, this treatment has not been shown to reduce mortality, as compared with amphotericin B monotherapy. 2 , 3 Flucytosine is frequently unavailable where the disease burden is greatest, and concerns about cost and side effects have limited its use in resource-poor settings. 4 Fluconazole is readily available, is associated with low rates of adverse events, and has good penetration into cerebrospinal . . .

Adjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone. The kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations were studied in a subset of HIV uninfected adults (n = 37) with TBM recruited to a randomized, placebo-controlled trial of adjuvant dexamethasone. Analysis followed a pre-defined plan. Dexamethasone significantly reduced CSF MMP-9 concentrations in early follow up samples (median 5 days (range 3-8) of treatment), but had no significant influence on other MMPs/TIMPs. Additionally CSF MMP-9 concentration was strongly correlated to concomitant CSF neutrophil count. Dexamethasone decreased CSF MMP-9 concentrations early in treatment and this may represent one mechanism by which corticosteroids improve outcome in TBM. The strong correlation between CSF MMP-9 and neutrophil count suggests that polymorphonuclear leukocytes may play a central role in the early pathogenesis of TBM.

IntroductionTDuring COVID-19 pandemic, it was noticed that it was students who were mostly affected by the changes that aroused because of the pandemic. The interesting part is whether students’ well-being could be associated with their fields of study as well as coping strategies.ObjectivesIn this study, we aimed to assess 1) the mental health of students from nine countries with a particular focus on depression, anxiety, and stress levels and their fields of study, 2) the major coping strategies of students after one year of the COVID-19 pandemic.MethodsWe conducted an anonymous online cross-sectional survey on 12th April – 1st June 2021 that was distributed among the students from Poland, Mexico, Egypt, India, Pakistan, China, Vietnam, Philippines, and Bangladesh. To measure the emotional distress, we used the Depression, Anxiety, and Stress Scale-21 (DASS-21), and to identify the major coping strategies of students - the Brief-COPE.ResultsWe gathered 7219 responses from students studying five major studies: medical studies (N=2821), social sciences (N=1471), technical sciences (N=891), artistic/humanistic studies (N=1094), sciences (N=942). The greatest intensity of depression (M=18.29±13.83; moderate intensity), anxiety (M=13.13±11.37; moderate intensity ), and stress (M=17.86±12.94; mild intensity) was observed among sciences students. Medical students presented the lowest intensity of all three components - depression (M=13.31±12.45; mild intensity), anxiety (M=10.37±10.57; moderate intensity), and stress (M=13.65±11.94; mild intensity). Students of all fields primarily used acceptance and self-distraction as their coping mechanisms, while the least commonly used were self-blame, denial, and substance use. The group of coping mechanisms the most frequently used was ‘emotional focus’. Medical students statistically less often used avoidant coping strategies compared to other fields of study. Substance use was only one coping mechanism that did not statistically differ between students of different fields of study. Behavioral disengagement presented the highest correlation with depression (r=0.54), anxiety (r=0.48), and stress (r=0.47) while religion presented the lowest positive correlation with depression (r=0.07), anxiety (r=0.14), and stress (r=0.11).Conclusions1) The greatest intensity of depression, anxiety, and stress was observed among sciences students, while the lowest intensity of those components was found among students studying medicine.2) Not using avoidant coping strategies might be associated with lower intensity of all DASS components among students.3) Behavioral disengagement might be strongly associated with greater intensity of depression, anxiety, and stress among students.4) There was no coping mechanism that provided the alleviation of emotional distress in all the fields of studies of students.Disclosure of InterestNone Declared

Tumor suppressor p53 has a key role in maintaining genomic stability and preventing tumorigenesis through its regulation of cellular stress responses, including apoptosis, cell cycle arrest and senescence. To ensure its proper levels and functions in cells, p53 is tightly regulated mainly through post-translational modifications, such as ubiquitination. Here, we identified E3 ubiquitin ligase TRIM32 as a novel p53 target gene and negative regulator to regulate p53-mediated stress responses. In response to stress, such as DNA damage, p53 binds to the p53 responsive element in the promoter of the TRIM32 gene and transcriptionally induces the expression of TRIM32 in cells. In turn, TRIM32 interacts with p53 and promotes p53 degradation through ubiquitination. Thus, TRIM32 negatively regulates p53-mediated apoptosis, cell cycle arrest and senescence in response to stress. TRIM32 is frequently overexpressed in different types of human tumors. TRIM32 overexpression promotes cell oncogenic transformation and tumorigenesis in mice in a largely p53-dependent manner. Taken together, our results demonstrated that as a novel p53 target and a novel negative regulator for p53, TRIM32 has an important role in regulation of p53 and p53-mediated cellular stress responses. Furthermore, our results also revealed that impairing p53 function is a novel mechanism for TRIM32 in tumorigenesis.

AbstractObjectivesTo evaluate the effect of lateral versus supine positioning on incidence of hypoxaemia in sedated patients and to provide evidence based recommendations for respiratory strategies.DesignProspective, multicentre, randomised controlled trial.Setting14 tertiary hospitals in China, July to November 2024.Participants2159 adults (≥18 years) who underwent sedation.InterventionsSedated patients were randomly assigned (1:1) to receive either lateral positioning or conventional supine positioning, stratified by study centres.Main outcome measuresThe primary outcome was incidence of hypoxaemia (peripheral oxygen saturation (SpO2) ≤90%) within the first 10 minutes after positioning. Secondary outcomes included airway rescue interventions, incidence of severe hypoxaemia (SpO2 ≤85%), lowest oxygen saturation recorded, length of stay in the post-anaesthesia care unit, and safety measures (eg, bradycardia, tachycardia, hypotension, new onset arrhythmia). Analyses were performed on an intention-to-treat basis.ResultsOf 2159 patients randomised, 2143 were included in the primary analysis. The mean age of the patients was 53.1 years, mean body mass index was 23.9, and 53.7% (1150/2143) were women. The incidence of hypoxaemia was significantly lower in the lateral group compared with supine group (5.4% (58/1073) v 15.0% (161/1070); adjusted risk ratio 0.36, 95% confidence interval (CI) 0.27 to 0.49; P<0.001). Compared with patients in the supine group, patients in the lateral group required fewer airway rescue interventions (6.3% (68/1073) v 13.8% (148/1070); adjusted risk ratio 0.46, 0.34 to 0.61; P<0.001), had a lower incidence of severe hypoxaemia (0.7% (8/1073) v 4.8% (51/1070); adjusted risk ratio 0.16, 0.07 to 0.33; P<0.001), and had a higher mean lowest SpO2 level (96.9% v 95.7%, absolute adjusted mean difference 1.20%, 95% CI 0.87% to 1.54%; P<0.001). Additionally, length of stay in the post-anaesthesia care unit was shorter in the lateral group (38.2 v 40.5 minutes; absolute adjusted mean difference −2.22 minutes; 95% CI −3.63 to −0.80; P=0.002). Safety outcomes were comparable between the groups, but tachycardia was less frequent in the lateral group.ConclusionsPlacing sedated adults in the lateral position significantly reduces the incidence and severity of hypoxaemia and decreases the need for airway rescue interventions without compromising safety. Given its simplicity and low cost, lateral positioning could offer advantages in remote or resource constrained clinical settings. Further replication studies targeting patients with advanced age and high body mass index are needed to improve the generalisability of the findings.Trial registrationClinicalTrials.gov NCT06459167.

In this randomized, placebo-controlled trial involving 435 adolescents and adults with meningitis in Vietnam, the use of adjunctive dexamethasone did not reduce the rate of death or disability at 6 months. In subgroup analyses, a benefit of treatment was seen in patients with confirmed bacterial meningitis, whereas harm was identified in those with probable bacterial meningitis. In this trial in Vietnam, the use of adjunctive dexamethasone did not reduce the rate of death or disability at 6 months. In subgroup analyses, a benefit of treatment was seen in patients with confirmed bacterial meningitis, whereas harm was identified in those with probable bacterial meningitis. Pyogenic bacterial meningitis has neurologic sequelae or is fatal in 30% of affected patients. 1 Animal models of the disease suggest that the subarachnoid inflammatory response contributes to morbidity and mortality 2 , 3 and that corticosteroids may improve the outcome by attenuating this response. However, confirming this effect in humans has proved difficult. 4 We conducted a double-blind, placebo-controlled trial in Vietnam to determine whether adjunctive dexamethasone improves the outcome in adolescents and adults with bacterial meningitis. A meta-analysis of randomized, controlled trials of corticosteroids for bacterial meningitis that were reported between 1966 and 2001 concluded that corticosteroids reduced the rates of death, . . .

An improved prime editing system precisely corrected a 14-bp deletion in the rc gene of white rice, restoring the production of brown pigments.KEY MESSAGEAn improved prime editing system precisely corrected a 14-bp deletion in the rc gene of white rice, restoring the production of brown pigments.

Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8 + T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.

Background Most cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome. Methods A prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome. Results 57 patients were studied. Cryptococcus neoformans var grubii molecular type VN1 caused 70% of infections; C. gattii accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age ≥ 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for C. neoformans var grubii compared with C. gattii (p < 0.001 and p = 0.01 respectively). Conclusion In HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to C. neoformans var grubii . The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear.