Differential effects of high-definition transcranial direct current stimulation (HD-tDCS) on attentional guidance by working memory in males with substance use disorder according to memory modality.

Information stored in working memory can guide perception selection, and this process is modulated by cognitive control. Although previous studies have demonstrated that neurostimulation over the left dorsolateral prefrontal cortex (lDLPFC) contributes to restore cognitive control among individuals with substance use disorder (SUD), there remains an open question about the potential stimulation effects on memory-driven attention. To address this issue, the present study adopted a combined working memory/attention paradigm while employing high-definition transcranial direct current stimulation (HD-tDCS) to stimulate the lDLPFC. Observers were asked to maintain visual or audiovisual information in memory while executing a search task, while the validity of the memory contents for the subsequent search task could be either invalid or neutral. The results showed a faint memory-driven attentional suppression effect in sham stimulation only under the audiovisual condition. Moreover, anodal HD-tDCS facilitated attentional suppression effect in both the strength and temporal dynamics under the visual-only condition, whereas the effect was impaired or unchanged under the audiovisual condition. Surprisingly, cathodal HD-tDCS selectively improved temporal dynamics of the attentional suppression effect under the audiovisual condition. The present study revealed the differential enhancement of HD-tDCS on cognitive control over visual and audiovisual memory-driven attention among individuals with SUD.

Decellularized human amniotic membrane scaffolds: influence on the biological behavior of dental pulp stem cells.

OBJECTIVE: The objective of this study was to assess the characterization of human acellular amniotic membrane (HAAM) using various decellularization methods and their impact on the proliferation and differentiation of human dental pulp stem cells (DPSCs). The goal was to identify scaffold materials that are better suited for pulp regeneration. METHODS: Six different decellularization methods were used to generate the amniotic membranes. The characteristics of these scaffolds were examined through hematoxylin and eosin (H&E) staining, scanning electron microscopy (SEM), and immunohistofluorescence staining (IHF). The DPSCs were isolated, cultured, and their capacity for multidirectional differentiation was verified. The third generation (P3) DPSCs, were then combined with HAAM to form the decellularized amniotic scaffold-dental pulp stem cell complex (HAAM-DPSCs complex). Subsequently, the osteogenic capacity of the HAAM-DPSCs complex was evaluated using CCK8 assay, live-dead cell staining, alizarin red and alkaline phosphatase staining, and real-time quantitative PCR (RT-PCR). RESULTS: Out of the assessed decellularization methods, the freeze-thaw + DNase method and the use of ionic detergent (CHAPS) showed minimal changes in structure after decellularization, making it the most effective method. The HAAM-DPSCs complexes produced using this method demonstrated enhanced biological properties, as indicated by CCK8, alizarin red, alkaline phosphatase staining, and RT-PCR. CONCLUSION: The HAAM prepared using the freeze-thaw + DNase method and CHAPS methods exhibited improved surface characteristics and significantly enhanced the proliferation and differentiation capacity of DPSCs when applied to them. The findings, therefore demonstrate the capacity for enhanced pulp regeneration therapy.

Flavonoid Compounds in Hippophae rhamnoides L. Protect Endothelial Cells from Oxidative Damage Through the PI3K/AKT-eNOS Pathway.

Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT-eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4-2-1, Fr.4-2-2 and Fr.4-2-3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K-AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4-2-1 exerted its antioxidant effects by modulating the PI3K/AKT-eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress-induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.

Effects of Novel Nanoparticulate Bioceramic Endodontic Material on Human Dental Pulp Stem Cells In Vitro.

OBJECTIVES: This study aimed to investigate the in vitro effects of root canal filling and repair paste (nRoot BP) on human dental pulp stem cells (hDPSCs). METHODS: The effects of nRoot BP and iRoot BP Plus on the adhesion, proliferation, migration, and differentiation of hDPSCs were examined in vitro for 72 hours. The adhesion of cells was observed using immunofluorescence rhodamine ghost pen cyclic peptide staining and scanning electron microscopy (SEM). Cell density and changes in migration area were measured under a fluorescence inverted microscope. Fluorescent quantitative PCR was performed to detect genes related to odontogenesis and osteogenesis. RESULTS: Cells adhering to the surfaces of nRoot BP and iRoot BP Plus exhibited similar irregular polygonal morphologies, with cells extending irregular pseudopods to adhere to the materials. CCK-8 results indicated that the density of living cells for nRoot BP and iRoot BP Plus was lower than that of the blank control group at 3 and 5 days of culture. There was no significant difference in cell migration between the groups (P > .05). The migration ability of iRoot BP Plus and nRoot BP was similar to that of the control group. Both nRoot BP and iRoot BP Plus increased the expression of the RUNX2 gene, but there was no significant difference between the groups (P < .05). Furthermore, both nRoot BP and iRoot BP Plus downregulated the expression of the DSPP gene, with no significant difference between them (P > .05). CONCLUSIONS: nRoot BP exhibited a slight inhibition of hDPSC proliferation but did not affect the adhesion and migration of hDPSCs. The impact of nRoot BP on the osteogenic and odontogenic differentiation of hDPSCs was similar to that of iRoot BP Plus.

Development and validation of the Convalescence Symptom Assessment Scale for EsophageCtomy patients.

AIM: A specific, valid and reliable measure is much needed to dynamically assess the recovery of symptoms in oesophagectomy patients. This study describes developing and validating the Convalescent Symptom Assessment Scale for oesophagectomy patients (CSAS_EC). DESIGN: An instrument development and cross-sectional validation study was conducted. METHODS: This study consists of two components: instrument development and psychometric tests. In instrument development, the literature review, qualitative interviews, Delphi method expert consultation and face validation were used to develop and refine scale content. In psychometric tests, the clinical test version scale was used to conduct a cross-sectional in the thoracic surgery department from 17 June to 20 November 2022. The Classical Test Theory and Multidimensional Item Response Theory (MIRT) analyses examined psychometric properties. RESULTS: In instrument development, literature review (n = 20), qualitative interviews (n = 21), expert consultation (n = 12) and pre-survey (n = 15) led to the development of the clinical test version scale. In psychometric tests, a total of 331 participants were enrolled. Confirmatory factor analysis and MIRT analysis verified that a model with 28 items in four dimensions was good. The four dimensions were early recovery symptoms, late recovery symptoms, persistent present symptoms and psychosocial symptoms. The Cronbach's α is 0.827. The validity and reliability were demonstrated to be acceptable. CONCLUSIONS: The CSAS_EC scale can be used as a tool to evaluate the recovery status of oesophagectomy patients.

Pitch Improvement in Attentional Blink: A Study across Audiovisual Asymmetries.

Attentional blink (AB) is a phenomenon in which the perception of a second target is impaired when it appears within 200-500 ms after the first target. Sound affects an AB and is accompanied by the appearance of an asymmetry during audiovisual integration, but it is not known whether this is related to the tonal representation of sound. The aim of the present study was to investigate the effect of audiovisual asymmetry on attentional blink and whether the presentation of pitch improves the ability to detect a target during an AB that is accompanied by audiovisual asymmetry. The results showed that as the lag increased, the subject's target recognition improved and the pitch produced further improvements. These improvements exhibited a significant asymmetry across the audiovisual channel. Our findings could contribute to better utilizations of audiovisual integration resources to improve attentional transients and auditory recognition decline, which could be useful in areas such as driving and education.

Preparation of PDA-GO/CS composite scaffold and its effects on the biological properties of human dental pulp stem cells.

Reduced graphene oxide (rGO) is an graphene oxide (GO) derivative of graphene, which has a large specific surface area and exhibited satisfactory physicochemical characteristics. In this experiment, GO was reduced by PDA to generate PDA-GO complex, and then PDA-GO was combined with Chitosan (CS) to synthesize PDA-GO/CS composite scaffold. PDA-GO was added to CS to improve the degradation rate of CS, and it was hoped that PDA-GO/CS composite scaffolds could be used in bone tissue engineering. Physicochemical and antimicrobial properties of the different composite scaffolds were examined to find the optimal mass fraction. Besides, we examined the scaffold's biocompatibility by Phalloidin staining and Live and Dead fluorescent staining.Finally, we applied ALP staining, RT-qPCR, and Alizarin red S staining to detect the effect of PDA-GO/CS on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). The results showed that PDA-GO composite was successfully prepared and PDA-GO/CS composite scaffold was synthesized by combining PDA-GO with CS. Among them, 0.3%PDA-GO/CS scaffolds improves the antibacterial activity and hydrophilicity of CS, while reducing the degradation rate. In vitro, PDA-GO/CS has superior biocompatibility and enhances the early proliferation, migration and osteogenic differentiation of hDPSCs. In conclusion, PDA-GO/CS is a new scaffold materialsuitable for cell culture and has promising application prospect as scaffold for bone tissue engineering.

Evaluation of the effectiveness of promoted psychological resilience intervention for oesophageal cancer patients in rural China: A randomized controlled study.

PURPOSE: The objective of this randomized controlled trial was to examine the effectiveness of promoted resilience intervention to facilitate resilience, self-efficacy, coping mode, and social support for oesophageal cancer patients in rural China. METHODS: A two-arm, parallel design, single-blinded, randomized controlled trial was conducted in a comprehensive tertiary hospital in Anhui from August 2021 to September 2022. A total of 82 oesophageal cancer patients were assigned to two groups via blocked randomization. The intervention group (n = 41) received the Promoted Psychological Resilience Intervention based on survivors' experiences and the control group (n = 41) received routine care. Study data were collected using the sociodemographic information, Connor-Davidson Resilience Scale, Strategies Used by People to Promote Health, Medical Coping Modes Questionnaire, and Perceived Social Support Scale. RESULTS: The groups were well-balanced at baseline. Post-intervention and three months after intervention, the resilience, self-efficacy, acceptance-resignation, and social support were all significantly different in the intervention and control groups (p < 0.05 for each). The main effect of group, time, and the interaction between group and time was statistically significant in the scores of resilience, self-efficacy, acceptance-resignation, and social support, except for the factor of self-determination and friends support (p < 0.05 for each). CONCLUSIONS: This study demonstrated that an intervention program based on the experiences of long-term oesophageal cancer survivors can promote patients' resilience.

The Mediating Effect of Resilience on the Relationship Between Symptom Burden and Anxiety/Depression Among Chinese Patients with Primary Liver Cancer After Liver Resection.

Purpose: Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression. Patients and Methods: A total of 223 postoperative PLC patients were recruited from two public hospitals in Anhui Province, China. All participants completed the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Connor-Davidson Resilience Scale (CD-RISC). The mediating effect of resilience was estimated using the bootstrap method via IBM SPSS AMOS 26.0. Results: The mean HADS score was 12.37 ± 6.03 points in postoperative PLC patients. Among these patients, 78 (34.98%) had anxiety, and 64 (28.70%) had depression, as indicated by a subscale score ≥ 8. Pearson correlation analysis revealed that anxiety/depression was positively associated with symptom burden (p < 0.05) and negatively associated with resilience (p < 0.05). Furthermore, resilience partially mediated the relationship between symptom burden and anxiety/depression (ß = 0.04; 95% confidence interval: 0.01-0.08). Conclusion: The levels of anxiety and depression in postoperative PLC patients should be decreased. Resilience partially mediated the relationship between symptom burden and anxiety/depression, but the indirect effect was much weaker than the direct effect of symptom burden on anxiety/depression. Consequently, rather than focusing primarily on resilience interventions, joint symptom-psychological interventions focusing on symptoms should be considered for patients with PLC after hepatectomy to reduce the levels of anxiety/depression.

A latent class analysis of resilience and its association with patient-reported symptoms in patients with esophageal cancer after esophagectomy.

Purpose: To identify the latent classes of resilience in patients with esophageal cancer after esophagectomy and develop a deeper understanding of the association between these classes and patient-reported symptoms. Background: China accounts for more than half of the global burden of esophageal cancer, and patients with esophageal cancer experience numerous symptoms that affect their quality of life and prognosis. Given that resilience is a key element that alleviates the progression of symptoms, it may represent a potential means of to enhancing cancer patients' physical and psychological well-being. Methods: The study was implemented in the thoracic surgery departments of three tertiary hospitals in eastern China. The participants were patients who were still hospitalized after esophagectomy. Data were gathered by self-report questionnaires, and a latent class analysis was utilized to identify different categories of resilience among the patients. Results: A total of 226 patients were recruited. The three classes of resilience identified included high strength and striving (53.5%), medium resilience but weak self-recovery (35.9%), and minimal tenacity and external support (10.6%). Patients with low income (OR = 12.540, p = 0.004) were more likely to be in the minimal tenacity and external support class. Patients without comorbidities (OR = 2.413, p = 0.013) and aged 66-70 years (OR = 4.272, p < 0.001) were more likely to be in the high strength and striving class. The patient-reported symptoms and symptom-related interference of patients after esophagectomy varied considerably among the three categories of resilience. Conclusion: Accurate interventions should be devised and executed according to the features of each type of resilience in patients after esophagectomy to maximize intervention efficacy. These findings highlight the important role of precision nursing.

A study on the transmission dynamics of COVID-19 considering the impact of asymptomatic infection.

The COVID-19 epidemic has been spreading around the world for nearly three years, and asymptomatic infections have exacerbated the spread of the epidemic. To analyse and evaluate the role of asymptomatic infections in the spread of the epidemic, we establish an improved COVID-19 infectious disease dynamics model. We fit the epidemic data in the four time periods corresponding to the selected 614G, Alpha, Delta and Omicron variants and obtain the proportion of asymptomatic persons among the infected persons gradually increased and with the increase of the detection ratio, the cumulative number of cases has dropped significantly, but the decline in the proportion of asymptomatic infections is not obvious. Therefore, in view of the hidden transmission of asymptomatic infections, the cooperation between various epidemic prevention and control policies is required to effectively curb the spread of the epidemic.

[The degradation of plastics and the production of polyhydroxyalkanoates (PHA)].

In recent years, the petroleum-based plastic pollution problem has been causing global attention. The idea of "degradation and up-cycling of plastics" was proposed for solving the environmental pollution caused by non-degradable plastics. Following this idea, plastics would be firstly degraded and then reconstructed. Polyhydroxyalkanoates (PHA) can be produced from the degraded plastic monomers as a choice to recycle among various plastics. PHA, a family of biopolyesters synthesized by many microbes, have attracted great interest in industrial, agricultural and medical sectors due to its biodegradability, biocompatibility, thermoplasticity and carbon neutrality. Moreover, the regulations on PHA monomer compositions, processing technology, and modification methods may further improve the material properties, making PHA a promising alternative to traditional plastics. Furthermore, the application of the "next-generation industrial biotechnology (NGIB)" utilizing extremophiles for PHA production is expected to enhance the PHA market competitiveness, promoting this environmentally friendly bio-based material to partially replace petroleum-based products, and achieve sustainable development with carbon-neutrality. This review summarizes the basic material properties, plastic upcycling via PHA biosynthesis, processing and modification methods of PHA, and biosynthesis of novel PHA.

A randomised controlled trial to improve the resilience of oesophageal cancer survivors in rural China: A study protocol.

AIM: To design a protocol based on the experiences of long-term survivors to facilitate resilience for oesophageal cancer patients in rural China. BACKGROUND: According to the latest Global Cancer Statistics Report, 604,000 new cases of oesophageal cancer were reported, of which over 60% of the disease burden is distributed in China. The incidence of oesophageal cancer in rural China (15.95/100,000) is twice as high as those in urban areas (7.59/100,000). To be sure, resilience can help patients better adapt to post-cancer life. But universal interventions involving improving the resilience of oesophageal cancer patients have much less been explored, especially for rural patients. METHODS: The two-arm, parallel design, non-blinded, randomised controlled trial will be implemented in 86 adults diagnosed with oesophageal cancer and will be randomly assigned to the control group or the intervention group via the blocked randomisation. The intervention group will undergo an intervention with one-on-one guidance from a nurse while viewing a CD of the experiences of long-term survivors with oesophageal cancer in rural areas. Every 2 weeks, a theme session will be introduced, and the entire intervention will continue for 12 weeks. Psychosocial variables (resilience, self-efficacy, coping mode and family support) will be surveyed at baseline, post-intervention and 3 months after the intervention. The paper complies with the Standard Protocol Items: Recommendations for Intervention Trials 2013 and Consolidated Standards of Reporting Trials guidelines for study protocols adapted for designing and reporting parallel group randomised trials. CONCLUSION: The intervention programme transitions from hospitalisation to discharge, which includes one-on-one interventions by medical personnel and a portable CD describing the experiences of long-term survivors with rural oesophageal cancer. Once the intervention's effectiveness is proven, this protocol will provide psychological support for massive oesophageal cancer patients. RELEVANCE TO CLINICAL PRACTICE: The intervention programme may be used as an auxiliary therapy to promote patients' postoperative psychological rehabilitation. This programme has the advantages of being cost-effective, flexible, accessible, and convenient and can be implemented without the limitation of time, place and clinical medical staff. TRIAL REGISTRATION: The Chinese Clinical Trial Registration number is ChiCTR2100050047. Registered on 16 August 2021.

Effect of Target Semantic Consistency in Different Sequence Positions and Processing Modes on T2 Recognition: Integration and Suppression Based on Cross-Modal Processing.

In the rapid serial visual presentation (RSVP) paradigm, sound affects participants' recognition of targets. Although many studies have shown that sound improves cross-modal processing, researchers have not yet explored the effects of sound semantic information with respect to different locations and processing modalities after removing sound saliency. In this study, the RSVP paradigm was used to investigate the difference between attention under conditions of consistent and inconsistent semantics with the target (Experiment 1), as well as the difference between top-down (Experiment 2) and bottom-up processing (Experiment 3) for sounds with consistent semantics with target 2 (T2) at different sequence locations after removing sound saliency. The results showed that cross-modal processing significantly improved attentional blink (AB). The early or lagged appearance of sounds consistent with T2 did not affect participants' judgments in the exogenous attentional modality. However, visual target judgments were improved with endogenous attention. The sequential location of sounds consistent with T2 influenced the judgment of auditory and visual congruency. The results illustrate the effects of sound semantic information in different locations and processing modalities.

The complete chloroplast genome sequence of Rubus irritans Focke 1910 (Rosaceae).

Rubus irritans Focke is a type of tonifying kidney-essence herb used in China. We present the complete chloroplast (cp) genome of R. irritans, a member of the genus Rubus. The complete cp genome of R. irritans was 155,286 bp long and consisted of an 84,613 bp long large single-copy (LSC) region, an 18,697 bp long SSC region, and a pair of 25,988 bp long inverted repeats (IR). Furthermore, the plastid genome contained 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the genome was 37.29%. Based on the complete cp genome, phylogenetic analysis revealed that R. irritans is closely related to R. amabilis.

A comprehensive single cell data analysis of lymphoblastoid cells reveals the role of super-enhancers in maintaining EBV latency.

We probed the lifecycle of Epstein-Barr virus (EBV) on a cell-by-cell basis using single cell RNA sequencing (scRNA-seq) data from nine publicly available lymphoblastoid cell lines (LCLs). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350- LMP1hi cells, expressed high levels of HIF1A and was transcriptionally regulated by HIF1-α. Treatment of LCLs with Pevonedistat, a drug that enhances HIF1-α signaling, markedly induced this cluster. The second cluster, containing GP350+ LMP1hi cells, expressed EBV lytic genes. Host genes that are controlled by super-enhancers (SEs), such as transcription factors MYC and IRF4, had the lowest expression in this cluster. Functionally, the expression of genes regulated by MYC and IRF4 in GP350+ LMP1hi cells were lower compared to other cells. Indeed, induction of EBV lytic reactivation in EBV+ AKATA reduced the expression of these SE-regulated genes. Furthermore, CRISPR-mediated perturbation of the MYC or IRF4 SEs in LCLs induced the lytic EBV gene expression, suggesting that host SEs and/or SE target genes are required for maintenance of EBV latency. Collectively, our study revealed EBV-associated heterogeneity among LCLs that may have functional consequence on host and viral biology.

Estimating New Cases Among Athletes During the Winter Olympics Based on a Dynamic Model - Beijing, China, February 2022.

Introduction: Since first appearing in late 2021, the Omicron variant has spread rapidly around the world. Nevertheless, the XXIV Winter Olympic Games (WOG) were held in Beijing in February 2022, which undoubtedly posed a huge challenge to domestic epidemic prevention and control. Methods: To analyze and evaluate the spread of the epidemic within the closed-loop management of the Beijing 2022 WOG, an improved dynamics model was established. Using the known dynamics parameters, the new daily cases and final members of quarantined people were predicted, and the influence of different factors on the change of the number of quarantined people was analyzed. Results: When the proportion of exposed persons being detected and the degree of admixture between the two populations varied between 0.5 and 0.9, there was little change in the daily predicted number of new cases and the final number of quarantined patients. As the initial value of the exposed among inbound personnel increased, the final size of quarantined patients increased proportionally. Discussion: From the analysis results, detecting potential virus carriers at the entry stage is the most effective way to control the spread of the epidemic within the closed-loop management of the Beijing 2022 WOG.

Effects of Tai Chi and Walking Exercise on Emotional Face Recognition in Elderly People: An ERP Study.

Both tai chi and walking can improve the physical health of the elderly, but the effect on the emotional cognitive function of the elderly is unclear. To investigate the effect of long-term walking and tai chi exercise on the emotional cognitive function of the elderly, 63 subjects were recruited in this study according to age and exercise habits, including 16 in the youth control group, 15 in the elderly non-exercise control group, 17 in the elderly walking group, and 18 in the elderly tai chi group. The "learning-test paradigm" of emotional faces was used to measure the subjects' ability to recognize and remember emotional (negative and neutral) faces. Behavioral and EEG data were recorded during the learning and testing phases. The results showed that there is aging in emotional cognition in older adults compared with younger adults. Long-term walking and tai chi exercise can delay the deterioration of emotional cognitive function in older adults to some extent. Both walking and tai chi exercise can delay the decline in aging-related emotional face recognition function to some extent. Walking exercise can delay the decline in aging-related emotional face memory function to some extent.

Rapid Quantification of Polyhydroxyalkanoates Accumulated in Living Cells Based on Green Fluorescence Protein-Labeled Phasins: The qPHA Method.

Polyhydroxyalkanoates (PHAs) are microbial polyesters that have the potential to replace nonbiodegradable petroplastics. A real-time in situ PHA quantification method has long been awaited to replace the traditional method, which is time- and labor-consuming. Quantification of PHA in living cells was finally developed from fluorescence intensities generated from the green fluorescence protein (GFP) fused with the Halomonas bluephagenesis phasin proteins. Phasins PhaP1 and PhaP2 were used to fuse with GFP, which reflected PHA accumulation with an R-square of over 0.9. Also, a standard correlation was established to calculate PHA contents based on the fluorescence and cell density recorded via a microplate reader with an R-square of over 0.95 when grown on various substrates. The PhaP2-GFP containing H. bluephagenesis was applied successfully to quantify PHA synthesis in a 7.5 L fermenter with high precision. Moreover, the method was found to be feasible in non-natural PHA producers such as Escherichia coli, demonstrating its broad applicability.

Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells.

The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.