Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Altered brain function in classical trigeminal neuralgia patients: ALFF, ReHo, and DC static- and dynamic-frequency study.

The present study aimed to clarify the brain function of classical trigeminal neuralgia (CTN) by analyzing 77 CTN patients and age- and gender-matched 73 healthy controls (HCs) based on three frequency bands of the static and dynamic amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality (sALFF, sReHo, sDC, dALFF, dReHo, and dDC). Compared to HCs, the number of altered brain regions was different in three frequency bands, and the classical frequency band was most followed by slow-4 in CTN patients. Cerrelellum_8_L (sReHo), Cerrelellum_8_R (sDC), Calcarine_R (sDC), and Caudate_R (sDC) were found only in classical frequency band, while Precuneus_L (sALFF) and Frontal_Inf_Tri_L (sReHo) were found only in slow-4 frequency band. Except for the above six brain regions, the others overlapped in the classical and slow-4 frequency bands. CTN seriously affects the mental health of patients, and some different brain regions are correlated with clinical parameters. The static and dynamic indicators of brain function were complementary in CTN patients, and the changing brain regions showed frequency specificity. Compared to slow-5 frequency band, slow-4 is more consistent with the classical frequency band, which could be valuable in exploring the pathophysiology of CTN.

Dental data challenge the ubiquitous presence of Homo in the Cradle of Humankind.

The origins of Homo, as well as the diversity and biogeographic distribution of early Homo species, remain critical outstanding issues in paleoanthropology. Debates about the recognition of early Homo, first appearance dates, and taxonomic diversity within Homo are particularly important for determining the role that southern African taxa may have played in the origins of the genus. The correct identification of Homo remains also has implications for reconstructing phylogenetic relationships between species of Australopithecus and Paranthropus, and the links between early Homo species and Homo erectus. We use microcomputed tomography and landmark-free deformation-based three-dimensional geometric morphometrics to extract taxonomically informative data from the internal structure of postcanine teeth attributed to Early Pleistocene Homo in the southern African hominin-bearing sites of Sterkfontein, Swartkrans, Drimolen, and Kromdraai B. Our results indicate that, from our sample of 23 specimens, only 4 are unambiguously attributed to Homo, 3 of them coming from Swartkrans member 1 (SK 27, SK 847, and SKX 21204) and 1 from Sterkfontein (Sts 9). Three other specimens from Sterkfontein (StW 80 and 81, SE 1508, and StW 669) approximate the Homo condition in terms of overall enamel-dentine junction shape, but retain Australopithecus-like dental traits, and their generic status remains unclear. The other specimens, including SK 15, present a dominant australopith dental signature. In light of these results, previous dietary and ecological interpretations can be reevaluated, showing that the geochemical signal of one tooth from Kromdraai (KB 5223) and two from Swartkrans (SK 96 and SKX 268) is consistent with that of australopiths.

S-Nitrosylation of the histone deacetylase HDA19 stimulates its activity to enhance plant stress tolerance in Arabidopsis.

Arabidopsis histone deacetylase HDA19 is required for gene expression programs of a large spectrum of plant developmental and stress-responsive pathways. How this enzyme senses cellular environment to control its activity remains unclear. In this work, we show that HDA19 is post-translationally modified by S-nitrosylation at 4 Cysteine (Cys) residues. HDA19 S-nitrosylation depends on the cellular nitric oxide level, which is enhanced under oxidative stress. We find that HDA19 is required for cellular redox homeostasis and plant tolerance to oxidative stress, which in turn stimulates its nuclear enrichment, S-nitrosylation and epigenetic functions including binding to genomic targets, histone deacetylation and gene repression. The Cys137 of the protein is involved in basal and stress-induced S-nitrosylation, and is required for HDA19 functions in developmental, stress-responsive and epigenetic controls. Together, these results indicate that S-nitrosylation regulates HDA19 activity and is a mechanism of redox-sensing for chromatin regulation of plant tolerance to stress.

Complete mitochondrial genome of Melia azedarach L., reveals two conformations generated by the repeat sequence mediated recombination.

Melia azedarach is a species of enormous value of pharmaceutical industries. Although the chloroplast genome of M. azedarach has been explored, the information of mitochondrial genome (Mt genome) remains surprisingly limited. In this study, we used a hybrid assembly strategy of BGI short-reads and Nanopore long-reads to assemble the Mt genome of M. azedarach. The Mt genome of M. azedarach is characterized by two circular chromosomes with 350,142 bp and 290,387 bp in length, respectively, which encodes 35 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes. A pair of direct repeats (R1 and R2) were associated with genome recombination, resulting in two conformations based on the Sanger sequencing and Oxford Nanopore sequencing. Comparative analysis identified 19 homologous fragments between Mt and chloroplast genome, with the longest fragment of 12,142 bp. The phylogenetic analysis based on PCGs were consist with the latest classification of the Angiosperm Phylogeny Group. Notably, a total of 356 potential RNA editing sites were predicted based on 35 PCGs, and the editing events lead to the formation of the stop codon in the rps10 gene and the start codons in the nad4L and atp9 genes, which were verified by PCR amplification and Sanger sequencing. Taken together, the exploration of M. azedarach gap-free Mt genome provides a new insight into the evolution research and complex mitogenome architecture.

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Constitutively expressed small heat shock protein LsHsp21.5 not only enhances heat tolerance but also helps to maintain reproduction in female Laodelphax striatellus.

Coping with stressful conditions and maintaining reproduction are two key biological processes that affect insect population dynamics. Small heat shock proteins (sHSPs) are involved in the stress response and the development of insects. The sHsp gene Laodelphax striatellus (Hemiptera: Delphacidae) sHsp 21.5 (LsHsp21.5) showed constitutive, stage- and organ-specific expression in L. striatellus, a pest that damages cultivated rice in east Asia. The expression of LsHsp21.5 was highest in the ovary, with 43.60, 12.99 and 1.45 time higher expression here than in the head, gut and female fat bodies, respectively. The expression of this gene was weakly affected by heat or cold shock. The gene provided in vitro protection against heat damage to malate dehydrogenase and in vivo protection against heat stress in Escherichia coli (Enterobacteriales: Enterobacteriaceae) BL21(DE3) and L. striatellus. Moreover, L. striatellus reproduction decreased by 1.85 times when the expression of LsHsp21.5 was inhibited by RNA interference. The expression of some genes related to reproduction, such as the homologous gene of chorion protein, also declined. These results suggest that LsHsp21.5 expression not only protects other proteins against stress but also helps maintain the stable expression of some reproduction-related genes under non-stressful conditions, with impacts on L. striatellus fecundity.

Development and Validation of a Fusion Model Based on Carotid Plaques and White Matter Lesion Burden Imaging Characteristics to Evaluate Ischemic Stroke Severity in Symptomatic Patients.

BACKGROUND: The diagnostic value of carotid plaque characteristics based on higher-resolution vessel wall MRI (HRVW-MRI) combined with white matter lesion (WML) burden for the risk of ischemic stroke is unclear. PURPOSE: To combine carotid plaque features and WML burden to construct a hybrid model for evaluating ischemic stroke severity and prognosis in patients with symptomatic carotid artery stenosis. STUDY TYPE: Retrospective. SUBJECTS: One hundred and ninty-three patients with least one confirmed carotid atherosclerotic stenosis ≥30% and cerebrovascular symptoms within the last 2 weeks (136 in the training cohort and 57 in the test cohort). FIELD STRENGTH/SEQUENCE: 3.0T, T2-weighted fluid attenuated inversion recovery (T2-FLAIR) and diffusion-weighted imaging (DWI); HRVW-MRI: 3D T1-weighted variable flip angle fast spin-echo sequences (VISTA), T2-weighted VISTA, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP), and contrast-enhanced T1-VISTA. ASSESSMENT: The following features of the plaques or vessel wall were assessed by three MRI readers independently: calcification (CA), intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), ulceration, plaque enhancement (PE), maximum vessel diameter (Max VD), maximum wall thickness (Max WT), total vessel area (TVA), lumen area (LA), plaque volume, and lumen stenosis. WMLs were graded visually and categorized as absent-to-mild WMLs (Fazekas score 0-2) or moderate-severe WMLs (Fazekas score 3-6). WML volumes were quantified using a semiautomated volumetric analysis program. Modified Rankin scores (mRS) were assessed at 90 days, following an outpatient interview, or by telephone. STATISTICAL TESTS: LASSO-logistic regression analysis was performed to construct a model. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analyses, calibration curves, decision curve analyses, and clinical imaging curves. Conditional logistic regression analysis was used to explore the associations between the hybrid model-derived score and the modified Rankin Scale (mRS) score at 90 days. RESULTS: The model was constructed using five selected features, including IPH, plaque enhancement, ulceration, NWI, and total Fazekas score in deep WMLs (DWMLs). The hybrid model yielded an area under the curve of 0.92 (95% confidence interval [CI] 0.87-0.97) in the training cohort and 0.88 (0.80-0.96) in the test cohort. Furthermore, the hybrid model-derived score (odds ratio = 1.28; 95% CI 1.06-1.53) was independently associated with the mRS score 90 days after stroke. DATA CONCLUSIONS: The hybrid model constructed using MRI plaque characteristics and WML burden has potential to be an effective noninvasive method of assessing ischemic stroke severity. The model-derived score has promising utility in judging neurological function recovery. TECHNICAL EFFICACY: Stage 2.

Biobased Tannic Acid-Chitosan Composite Membranes as Reusable Adsorbents for Effective Enrichment of Phosphopeptides.

High-performance reusable materials from renewable resources are rare and urgently required in bioseparation. Herein, a series of tannic acid-chitosan composite membranes for the enrichment of phosphopeptides were fabricated by the freeze casting method. First, a tannic acid-chitosan composite membrane was acquired via the multiple hydrogen bonds between tannic acid and chitosan, which had a long-range aligned three-dimensional microstructure. Second, a covalent-hydrogen bond hybrid composite was also fabricated, with stable and aligned honeycomb-like microstructures that formed by the synergy of covalence and hydrogen bonding. Besides, a ternary composite membrane was "one-pot" synthesized by the copolymerization of tannic acid, chitosan, and Ti4+ ions, indicating the feasibility of involving metal ions in the composition of the polymer skeleton in place of additional modification steps. The as-prepared chitosan composite membranes exhibited excellent performance in the enrichment of phosphopeptides from ß-casein tryptic digest and human serum. Benefitting from the long-range aligned honeycomb-like structure coordinated by hydrogen bonds and covalent bonds, and a large number of pyrogallol functional groups provided by tannic acid, the covalent-hydrogen bond hybrid membrane showed excellent reusability and could be reused up to 16 times in phosphopeptide enrichment, as far as we know, which is the best reported result to date.

Altered trends of local brain function in classical trigeminal neuralgia patients after a single trigger pain.

OBJECTIVE: To investigate the altered trends of regional homogeneity (ReHo) based on time and frequency, and clarify the time-frequency characteristics of ReHo in 48 classical trigeminal neuralgia (CTN) patients after a single pain stimulate. METHODS: All patients underwent three times resting-state functional MRI (before stimulation (baseline), after stimulation within 5 s (triggering-5 s), and in the 30th min of stimulation (triggering-30 min)). The spontaneous brain activity was investigated by static ReHo (sReHo) in five different frequency bands and dynamic ReHo (dReHo) methods. RESULTS: In the five frequency bands, the number of brain regions which the sReHo value changed in classical frequency band were most, followed by slow 4 frequency band. The left superior occipital gyrus was only found in slow 2 frequency band and the left superior parietal gyrus was only found in slow 3 frequency band. The dReHo values were changed in midbrain, left thalamus, right putamen, and anterior cingulate cortex, which were all different from the brain regions that the sReHo value altered. There were four altered trends of the sReHo and dReHo, which dominated by decreased at triggering-5 s and increased at triggering-30 min. CONCLUSIONS: The duration of brain function changed was more than 30 min after a single pain stimulate, although the pain of CTN was transient. The localized functional homogeneity has time-frequency characteristic in CTN patients after a single pain stimulate, and the changed brain regions of the sReHo in five frequency bands and dReHo complemented to each other. Which provided a certain theoretical basis for exploring the pathophysiology of CTN.

A Comparative Analysis of the Clinical Efficacy of Sacubitril Valsartan Sodium and Enalapril in Patients with Non-Valvular Ejection Fraction Reduction in Heart Failure.

Objective: Heart failure is a common cardiovascular disease, and its prevalence is increasing year by year. For patients with heart failure combined with non-valvular reduced ejection fraction, drug therapy has always been a key treatment. This study aimed to explore the clinical efficacy of sacubitril valsartan sodium and enalapril in such patients. Methods: Study design: This study used a prospective observational design. From February 2020 to February 2022, we included 123 patients with non-valvular heart failure and reduced ejection fraction who were treated in Xingtai Third Hospital. Patients were divided into two groups according to the treatment plan: Group A (n=61) received enalapril, and Group B (n=62) received nifedipine. All patients received conventional treatment. We compared the efficacy of the two groups of patients 8 weeks after treatment. During the study, the laboratory indicators, echocardiographic indicators, cardiovascular markers, and possible adverse reactions of the two groups of patients before and after treatment were recorded. Results: After 8 weeks of treatment, the effective rate of group B was higher than group A (P < .05). There were no differences in the levels of total protein, total bilirubin, total cholesterol and serum creatinine between the two groups before and after treatment (P > .05). The serum creatinine level in the two groups after treatment was higher than that before treatment, and the level in group B was lower than that in group A (P < .05). There were no statistically significant differences in the levels of total protein, total bilirubin and total cholesterol between the two groups before and after treatment (P > .05), and there was no statistically significant difference in the level of serum creatinine between the two groups before treatment (P > .05), and the level of serum creatinine after treatment was higher than that before treatment, and the level of group B was lower than that of group A (P < .05). Before treatment, there was no significant difference in the levels of high-sensitive troponin T and n-terminal brain natriuretic peptide and cyclic guanosine phosphate between the two groups (P > .05). After treatment, the levels of high-sensitive troponin T and N-terminal brain natriuretic peptide in the two groups were lower than those before treatment, and those in group B were lower than those in group A. The level of cyclic guanosine phosphate in group A was lower than that before treatment, the level of cyclic guanosine phosphate in group B was higher than that before treatment, and the level of group B was higher than that of group A (P < .05). The incidence of adverse cardiovascular events in group B was lower than that in group A (P < .05).In this study, the effective rate of treatment group B was significantly higher than that of treatment group A, indicating that treatment group B had a better therapeutic effect. In addition, there were no significant differences between the two groups in a series of biochemical parameters, but it is worth noting that after treatment, the serum creatinine level of group B was significantly lower than that of group A, which may indicate that the treatment of group B is not only more effective but also Reduces the risk of certain adverse cardiovascular events. Conclusion: The main findings of the study showed that Sacubitril valsartan sodium showed better clinical efficacy than enalapril in patients with heart failure and non-valvular reduced ejection fraction. Specifically, the drug significantly improved patients' kidney function, reduced cardiovascular marker levels, and reduced the incidence of adverse cardiovascular events. These findings have important clinical implications for guiding treatment selection in patients with heart failure.

Application of rapid on-site evaluation combined with flexible bronchoscopy in the diagnosis of lung lesions.

BACKGROUND: Pathology is considered the gold standard for the diagnosis of lung lesions, but the pathological result is relatively lagging and cannot provide real-time guidance for the biopsy procedure. OBJECTIVE: To investigate the potential application of rapid on-site evaluation (ROSE) during flexible bronchoscopy (FB) in the evaluation and diagnosis of lung lesions. PATIENTS AND METHODS: Consecutive patients who underwent FB for the diagnosis of lung lesions between August 2022 and February 2023 were included in this retrospective study. 294 patients underwent FB with ROSE, while 304 patients underwent FB without ROSE. The final pathological results and the number of patients undergoing repeat biopsies were recorded in both groups. Specifically, we conducted separate statistical analysis for patients undergoing different biopsy methods, including the endobronchial biopsy (EBB), radial probe endobronchial ultrasound transbronchial lung biopsy with guide sheath (r-EBUS-GS-TBLB), and the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to study the detailed roles that ROSE plays under different biopsy methods. RESULTS: The adequacy rate of biopsy specimens from the non-ROSE group was significantly lower than that of the ROSE group (259/281 = 92.17 % vs. 263/268 = 98.13 %, p = 0.001). Meanwhile, fewer patients underwent repeat biopsies in the ROSE group compared to the non-ROSE group (2/294 = 0.68 % vs. 10/304 = 3.29 %, p = 0.023). For the ROSE group, the consistency between ROSE diagnoses and final pathological diagnoses was 94.40 % (κ = 0.886), with 95.58 % for benign diseases and 93.55 % for malignant diseases. CONCLUSION: The utility of ROSE during FB increases the adequacy rate of biopsy specimens and thus decreases the need for repeat biopsies in patients with lung lesions to get a definite diagnosis. Moreover, the high consistency between ROSE diagnoses and final pathological diagnoses suggests that ROSE is a reliable tool for optimizing the diagnosis of lung lesions.

A Novel Frameshift Mutation(HBA2:C.337delC) Associated With α-Thalassemia Trait Detected by Next-Generation Sequencing in Southern China.

Here, we report a novel frameshift mutation caused by a single base deletion in exon 3 of the HBA2 gene (HBA2:c.337delC) detected by next-generation sequencing. The proband was a 26-year-old Chinese pregnant woman who originates from Hunan Province. Her mean corpuscular volume(MCV) and mean corpuscular hemoglobin (MCH) had a mild decrease. Capillary electrophoresis (CE) showed that both Hb A (97.8%) and Hb F (0.0%) values were within normal range, while the Hb A2 (2.2%) value was below normal. Sequence analysis of the α and ß-globin genes revealed a novel single base deletion at codon 112 (HBA2:c.337delC) in the heterozygous state, which resulted in a mild phenotype of α-thalassemia.

A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient.

Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and ß-globin chains and consequently cause clinical symptoms of ß-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with ß thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous ß0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of ß-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.

Effects of steam explosion pretreatment on the digestive properties and gut microbiota of Laminaria japonica polysaccharide.

BACKGROUND: Laminaria japonica polysaccharide, which is an important bioactive substance of Laminaria japonica with anti-inflammatory and antioxidant effects. In this study, the molecular weight, functional groups and surface morphology were investigated to evaluate the digestive properties of Laminaria japonica polysaccharide before and after steam explosion. RESULTS: The results indicated that the Laminaria japonica polysaccharide entered the large intestine to be utilized by the gut microbiota after passing through the oral, gastric and small intestinal. Meanwhile, Laminaria japonica polysaccharide of steam explosion promoted the growth of beneficial bacteria Phascolarctobacterium and Intestinimonas, and increased the content of acetic, propionic and butyric acids, which was 2.29-folds, 2.60-folds and 1.63-folds higher than the control group after 48 h of fermentation. CONCLUSION: This study reveals that the effect of steam explosion pretreatment on the digestion in vitro and gut microbiota of Laminaria japonica polysaccharide will provide a basic theoretical basis for the potential application of Laminaria japonica polysaccharide as a prebiotic in the food industry. © 2024 Society of Chemical Industry.

Sleep disorder experienced by healthcare nurses after terminating Zero-COVID-19 policy.

OBJECTIVE: Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. METHODS: 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. RESULTS: The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16-25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. CONCLUSION: Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.

Structural and functional brain alterations in Cushing's disease: A narrative review.

Neurocognitive and psychiatric symptoms are non-negligible in Cushing's disease and are accompanied by structural and functional alterations of the brain. In this review, we have summarized multimodal neuroimaging and neurophysiological studies to highlight the current and historical understandings of the structural and functional brain alterations in Cushing's disease. Specifically, structural studies showed atrophy of the gray matter, loss of white matter integrity, and demyelination in widespread brain regions. Functional imaging studies have identified three major functional brain connectome networks influenced by hypercortisolemia: the limbic network, the default mode network, and the executive control network. After endocrinological remission, atrophy of gray matter regions and the compromised functional network activities were partially reversible, and the widespread white matter integrity alterations cannot recover in years. In conclusion, Cushing's disease patients display structural and functional brain connectomic alterations, which provides insights into the neurocognitive and psychiatric symptoms observed in this disease.

Comprehensive genomic analyses of Vigna unguiculata provide insights into population differentiation and the genetic basis of key agricultural traits.

Vigna unguiculata is an important legume crop worldwide. The subsp. sesquipedalis and unguiculata are the two major types grown; the former is mainly grown in Asia to produce fresh pods, while the latter is mainly grown in Africa to produce seeds. Here, a chromosome-scale genome for subsp. sesquipedalis was generated by combining high-fidelity (HiFi) long-read sequencing with high-throughput chromosome conformation capture (Hi-C) technology. The genome size for all contigs and N50 were 594 and 18.5 Mb, respectively. The Hi-C interaction map helped cluster 91% of the contigs into 11 chromosomes. Genome comparisons between subsp. sesquipedalis and unguiculata revealed extensive genomic variations, and some variations resulted in gene loss. A germplasm panel with 315 accessions of V. unguiculata was resequenced, and a genomic variation map was constructed. Population structure and phylogenetic analyses suggested that subsp. sesquipedalis originated from subsp. unguiculata. Highly differentiated genomic regions were also identified, and a number of genes functionally enriched in adaptations were located in these regions. Two traits, pod length (PL) and pod width (PW), were observed for this germplasm, and genome-wide association analysis of these traits was performed. The quantitative trait loci (QTLs) for these two traits were identified, and their candidate genes were uncovered. Interestingly, genomic regions of PL QTLs also showed strong signals of artificial selection. Taken together, the results of this study provide novel insights into the population differentiation and genetic basis of key agricultural traits in V. unguiculata.

Clinical characteristics and therapeutic effects of checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

BACKGROUND: With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. METHODS: The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. RESULTS: 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. CONCLUSION: We found that glucocorticoid 1-2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.