Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine ...to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery of ChRmine, we demonstrate behavioral modulation without surgery, enabling implant-free deep brain optogenetics.
This empirical study is the first to analyze the response of Vietnamese cement plants to ISO 14001. The influence of ISO-compliant environmental management systems in Vietnam's cement industry was ...studied by examining the differences between pre- and post-certification and by comparing the results between certified and non-certified cement plants using a questionnaire and environmental indicators. The results of the management performance analysis demonstrated that the environmental awareness and attention in certified plants was better than in the non-certified plants. On operational performance, the results showed significant differences between the certified and non-certified plants on selected environmental indicators like dust, SO2 and NO2 as well as a significant improvement after the adoption of ISO 14001. As a whole, the certified plants performed better than the non-certified ones on management and operational aspects. This study has a twofold wider impact. It shows the methodological difficulties of assessing the impact of environmental management systems in situations of early implementation and low company awareness. Moreover, our findings indicate that ISO 14001 has the potential to improve organizations' environmental performance in a fast-developing country characterized by impressive industrial growth in recent decades.
•We examine changes in environmental performance pre and post 14001 certification.•We focus on differences between certified and non-certified cement factories.•The environmental awareness in certified group is better than in non-certified one.•Differences founded in environmental indicators among certified and non-certified.•Environmental indicators changed before and after adopting the ISO 14001.
Current drug treatments for epilepsy attempt to broadly restrict excitability to mask a symptom, seizures, with little regard for the heterogeneous mechanisms that underlie disease manifestation ...across individuals. Here, we discuss the need for a more complete view of epilepsy, outlining how key features at the cellular and microcircuit level can significantly impact disease mechanisms that are not captured by the most common methodology to study epilepsy, electroencephalography (EEG). We highlight how major advances in neuroscience tool development now enable multi-scale investigation of fundamental questions to resolve the currently controversial understanding of seizure networks. These findings will provide essential insight into what has emerged as a disconnect between the different levels of investigation and identify new targets and treatment options.
Farrell et al. discuss seizure mechanisms at the micro scale to highlight that such cellular-level information is necessary to explain epilepsy expression at the macroscale, where commonly used methodologies to locate seizure networks and guide interventions operate.
Microplastics in shoreline sediments were investigated from Da Nang beach for the first time. Sediment samples at the two depth strata (0–5 cm and 5–10 cm) at eight sites along the entire coast were ...collected for identifying the characteristics of microplastics, including their concentration, size, shape, color, and nature. The synthetic fiber was the predominant type of microplastics, accounting for 99.2% of the total items. Blue (59.9%) and white (22.9%) were the most common colors of the fibers. Synthetic fibers showed a homogenous distribution at all sampling sites with a mean concentration of 9238 ± 2097 items kg−1 d.w. Meanwhile, the fibers tended to concentrate much more at the surface stratum than the deeper stratum. A large number of synthetic fibers (81.9%) were in the size range of 300–2600 μm, which might pose a threat to marine biota and human health.
•Microplastic (300–5000 μm) were investigated in Da Nang beach, Vietnam.•Synthetic fibers predominated over other shapes with 99.2%.•A majority of fibers (81.9%) were in the size range of 300–2600 μm.•Mean synthetic fibers concentration in the sediments was 9238 ± 2097 items kg−1 d.w.•Higher fiber concentrations were found in 0–5 cm than in 5–10 cm.
•SCG-derived polysaccharides were produced through delignification and defatting.•Enzymatic hydrolysis was significantly enhanced in SCG-derived polysaccharides.•Manno-oligosaccharides, mannose, and ...bioethanol, were produced from SCG.
Spent coffee grounds (SCG) or coffee residue wastes (CRW) provide excellent raw material for mannose and bioethanol production. In this study, SCG were used to produce valuable biosugars, including oligosaccharides (OSs), manno-oligosaccharides (MOSs), mannose, and bioethanol. SCG were subjected to delignification and defatting, producing SCG-derived polysaccharides. Two-stage enzymatic hydrolysis (short- and long-term) was performed to produce short-chain manno-oligosaccharides (MOSs) and monosaccharides (MSs), respectively. From 100 g dry weight (DW) amounts of SCG, approximately 77 g delignified SCG and 61 g SCG-derived polysaccharides, amounts of 15.9 g of first biosugars (mostly MOSs), 25.6 g of second biosugars (mostly MSs), and 3.1 g of bioethanol, were recovered. This technique may aid in the production of high-value mannose and OSs from SCG and other lignocellulosic biomasses that contain specific polysaccharides.
Background
The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to ...peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunological changes in blood samples from a subset of peanut‐allergic individuals undergoing oral desensitization immunotherapy with AR101.
Methods
Blood samples obtained as part of enrollment screening and at multiple time points during PALISADE study were used to assess basophil and CD4+ T‐cell reactivity to peanut.
Results
The absence of clinical reactivity to the entry double‐blinded placebo‐controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T‐cell reactivity to peanut compared with DBPCFC reactors. At baseline, peanut‐reactive TH2A cells were observed in many but not all peanut‐allergic patients and their level in peripheral blood correlates with T‐cell reactivity to peanut and with serum peanut‐specific IgE and IgG4 levels. POIT reshaped circulating peanut‐reactive T‐cell responses in a subset‐dependent manner. Changes in basophil and T‐cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut‐reactive Treg cell frequency was observed between groups.
Conclusion
Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut‐reactive T effector cell responses supporting its potential as an immunomodulatory therapy.
CRTH2+ pTeff cells and CCR6+ pTeff cells represent two mutually exclusive, nonoverlapping cellular and molecular entities involved in food‐allergic diseases. Circulating CRTH2+ pTeff cells are mostly restricted to peanut‐allergic individuals who react to the 100 mg DBPCFC compared to those with lower clinical sensitivity to peanut. Changes in basophil and T‐cell responses to peanut closely parallel clinical benefits to POIT and resemble responses in those that did not react to the baseline 100 mg DBPCFC.Abbreviations: BAT‐EC50, concentration of allergen corresponding to 50% of maximal activation of basophils in basophil activation test; CCR6, C‐C motif chemokine receptor 6; CRTH2, chemoattractant receptor‐homologous molecule expressed on Th2 cells; DBPCFC, double‐blinded placebo‐controlled peanut challenge; FOXP3, forkhead box P3; freq, frequency; GATA3, GATA binding protein 3; HPGDS, hematopoietic prostaglandin D synthase; IFNG, interferon gamma; IL, interleukin; PALISADE, Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults; POIT, peanut oral immunotherapy; PPARG, peroxisome proliferator activated receptor alpha; pTeff, peanut‐reactive T cell; RORC, RAR related orphan receptor C; ST2, suppression of tumorigenicity 2
Cellulosic bioethanol production has been fraught with challenges, including fluctuations in feedstock supply, handling costs, pretreatment, enzymes, and other logistical problems. Most studies of ...lignocellulosic ethanol production have focused on a single type of biomass; however, full utilization of various lignocellulosic biomass sources might enhance bioethanol production and the economic feasibility of the biorefinery. The goal of this study was to evaluate the effectiveness of popping pretreatment on saccharification and fermentation for individual and mixed biomass. We then compared separate hydrolysis and fermentation (SHF) with simultaneous saccharification and fermentation (SSF) processing, with the aim of optimizing production of bioethanol from biomass. Saccharification efficiencies were increased significantly in all the popping-pretreated compared to the non-pretreated individual and mixed biomass. The SSF was superior compared to SHF processing. Our results indicated that the saccharification efficiencies of both individual and mixed biomass were improved after popping pretreatment; in particular, the production of bioethanol from mixed biomass was identified as a suitable approach for more extensive application.
Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating ...peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs.
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•We designed the peptide ReACp53 to halt aggregation of p53 in cells•ReACp53 rescues p53 transcription of target genes and restores apoptosis•In vivo ReACp53 halts progression and shrinks tumors bearing aggregation-prone p53•p53 aggregation in cancer is a target for therapy with ReACp53 as a lead compound
Using p53-mutant, high-grade, serous ovarian carcinoma as model systems, Soragni et al. show that a cell-penetrating peptide designed to inhibit p53 amyloid formation rescues p53 functions and reduces in vivo xenograft growth and metastasis.
Vietnam is undergoing a rapid epidemiological transition with a considerable burden of non-communicable diseases (NCDs), especially hypertension and diabetes (T2DM). Continuity of care (COC) is ...widely acknowledged as a benchmark for an efficient health system. This study aimed to determine the COC level for hypertension and T2DM within and across care levels and to investigate its associations with health outcomes and disease control.
A cross-sectional study was conducted on 602 people with T2DM and/or hypertension managed in primary care settings. We utilized both the Nijmegen continuity of care questionnaire (NCQ) and the Bice - Boxerman continuity of care index (COCI) to comprehensively measure three domains of COC: interpersonal, informational, and management continuity. ANOVA, paired-sample t-test, and bivariate and multivariable logistic regression analysis were performed to examine the predictors of COC.
Mean values of COC indices were: NCQ: 3.59 and COCI: 0.77. The proportion of people with low NCQ levels was 68.8%, and that with low COCI levels was 47.3%. Primary care offered higher informational continuity than specialists (p < 0.01); management continuity was higher within the primary care team than between primary and specialist care (p < 0.001). Gender, living areas, hospital admission and emergency department encounters, frequency of health visits, disease duration, blood pressure and blood glucose levels, and disease control were demonstrated to be statistically associated with higher levels of COC.
Continuity of primary care is not sufficiently achieved for hypertension and diabetes mellitus in Vietnam. Strengthening robust primary care services, improving the collaboration between healthcare providers through multidisciplinary team-based care and integrated care approach, and promoting patient education programs and shared decision-making interventions are priorities to improve COC for chronic care.
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