Search

Abstract During non-rapid eye movement (NREM) sleep, neural ensembles in the entorhinal-hippocampal circuit responsible for encoding recent memories undergo reactivation to facilitate the process of memory consolidation. This reactivation is widely acknowledged as pivotal for the formation of stable memory and its impairment is closely associated with memory dysfunction. To date, the neural mechanisms driving the reactivation of neural ensembles during NREM sleep remain poorly understood. Here, we show that the neural ensembles in the medial entorhinal cortex (MEC) that encode spatial experiences exhibit reactivation during NREM sleep. Notably, this reactivation consistently coincides with isolated theta waves. In addition, we found that the nucleus reuniens (RE) in the midline thalamus exhibits typical theta waves during NREM sleep, which are highly synchronized with those occurring in the MEC in male mice. Closed-loop optogenetic inhibition of the RE-MEC pathway specifically suppressed these isolated theta waves, resulting in impaired reactivation and compromised memory consolidation following a spatial memory task in male mice. The findings suggest that theta waves originating from the ventral midline thalamus play a role in initiating memory reactivation and consolidation during sleep.

Abstract This study aims to broaden the morphological scope of SDH-deficient renal cell carcinoma and to assist clinicians and pathologists in better understanding this entity to prevent misdiagnosis. This study used immunohistochemistry staining and the first-generation sequencing Sanger method for gene detection. It retrospectively analysed the clinical pathology, molecular characteristics, biological behaviour, and treatment information of one case of SDH-deficient renal cell carcinoma. The patient was a 57-year-old female with right back pain for more than 20 days and had no personal or family history of kidney tumours. In addition, the tumour cells had clear boundaries in morphology, and residual normal renal tubules could be seen around them. There were also ossification and adipose tissue around the tumour centre. The tumour cells were arranged in a glandular tubular and cord-like manner. Vacuolar and eosinophilic inclusion bodies could be observed in the cytoplasm. The nucleus was regular, the chromatin distribution was fine, and there were no obvious nucleoli. They were low-grade nuclei. In addition, no atypical mitosis or necrosis could been found. Furthermore, immunohistochemistry staining showed SDHB-negative and keratin 20 -positive tumour. Meanwhile, the first-generation sequencing also pointed out the presence of SDHB gene mutations in the tumour. After 12 months of follow-up, there was no evidence of disease recurrence in the patient. SDH-deficient renal cell carcinoma is a rare tumour associated with SDH gene germline mutations, and suspected cases should undergo SDHB immunohistochemistry staining. Most SDH-deficient renal cell carcinomas have a good prognosis, but undifferentiated cases require long-term follow-up.

Abstract Introduction Concentrated Growth Factor (CGF), rich in CD34 + stem cells, is widely used in treatments for androgenetic alopecia and skin rejuvenation due to its immune-modulating properties. Psoriasis, a chronic inflammatory skin condition, presents significant treatment challenges, particularly for patients who cannot use biologics due to conditions such as cancer and lesions resistant to treatments. The potential of CGF in treating psoriasis is promising, given its broad immunoregulatory effects which confirmed in our previous androgenetic alopecia work. Methods We evaluated the impact of CGF on IL-17 levels in two contexts: patients treated for androgenetic alopecia and a psoriasis mouse model. Twelve patients received three monthly injections of CGF, with serum IL-17 levels measured before and after treatment. In the psoriasis mouse model, groups were treated with CGF, and outcomes were assessed using the Psoriasis Area and Severity Index (PASI), skin barrier scores, histological analysis, and RNA sequencing. Additionally, in vitro experiments applied CD34 + cells from CGF to keratinocytes to measure levels of TNF-α, IFN-γ, IL-23, and IL-17. Results In patients with androgenetic alopecia, three monthly CGF injections resulted in significantly reduced serum IL-17 levels. In the psoriatic mouse model, CGF-treated groups exhibited lower PASI scores and improved skin barrier scores compared to controls. Histological analysis revealed enhanced skin characteristics, while RNA sequencing demonstrated downregulated IL-17 and upregulated CD34 expression, as well as improved expression of barrier-related genes. In vitro, the application of CD34 + cells from CGF to keratinocytes led to a significant reduction in TNF-α, IFN-γ, IL-23, and IL-17 levels, indicating strong anti-inflammatory effects. A clinical case of a psoriasis patient unresponsive to IL-23 therapy (Guselkumab) showed significant improvement following CGF treatment. Conclusion These findings indicate that CGF could serve as an effective and versatile treatment for psoriasis, especially for patients who have already undergone biologic therapies but continue to experience resistant lesions.

Abstract Background The purpose of this study was to explore the job burnout of primary healthcare workers in Guangzhou during the prevention and control of COVID-19 epidemic and its influencing factors from the perspective of institutional operation and management in 2021–2022. Methods A cross-sectional study involved 866 primary healthcare workers from different districts of Guangzhou, China. The Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS) was utilized to assess job burnout. From the perspective of organizational operation and management, the possible causes of job burnout among primary healthcare workers during COVID-19 have been categorized into 7 major aspects. Univariate and multivariate logistic regression analyses were conducted to identify influencing factors for job burnout in primary healthcare workers. Results The detection rate of job burnout among primary healthcare workers was 78.29%. Men (OR = 2.39) and whose institution was located in urban–rural fringe (OR = 1.56) were more likely to detect job burnout. Conversely, institution heads showed a lower risk of job burnout. From the perspective of institutional operation and management, workers who were not satisfied with personnel management (OR = 2.41), materials and vehicles (OR = 2.89), subsidies and compensation (OR = 2.18), humanistic care (OR = 2.11), superior management (OR = 8.32) were found to have a higher risk of job burnout. Conclusion The detection rate of job burnout among primary healthcare workers in Guangzhou was relatively high during the period of COVID-19. When there is another sudden major epidemic, the managers of institutions can focus on and deal with the problems related to the operation and management of institutions such as personnel management, materials and vehicles, subsidies and compensation, humanistic care, and superior management, so as to provide logistical support for the workers and alleviate their job burnout.

Background: Lactylation, a newly discovered PTM involving lactic acid, is linked to solid tumor proliferation and metastasis. Lymphoma patients exhibit high lactic acid levels, yet lactylation's role in lymphoma is underexplored. This study aimed to identify lactylation-related genes in lymphoma using tumor databases and assess their predictive value in patient prognosis through cell experiments and clinical specimens. Methods: Using TCGA and GEO datasets, we analyzed the expression levels of lactylation-related genes in diffuse large B-cell lymphoma patients. We also evaluated the prognostic significance of lactylation gene risk scores, exploring their impact on drug sensitivity and tumor immune function. Key lactylation-affecting genes were identified and functionally validated through cell experiments and mouse in vivo experiments. Additionally, the relationship between lactylation and lymphoma prognosis was examined in clinical specimens. Results: We identified 70 genes linked to diffuse large B-cell lymphoma prognosis from the lactylation-related gene set. Using clinical data and a COX regression algorithm, we developed an optimized lactylation Riskscore model. This model significantly correlated with prognosis and showed differences in immune cell infiltration, particularly macrophages. High-risk patients showed resistance to chemotherapy drugs but responded well to immunotherapy. HNRNPH1, a lactylation-related gene, influenced patient prognosis, apoptosis, cell cycle distribution in lymphoma cells, and tumor volume in mice. In lymphoma specimens, lactylation levels correlated with Bcl-2, C-myc, and P53 levels. Conclusions: Lactylation impacts diffuse large B-cell lymphoma prognosis, tumor immune function, and drug resistance. Our lactylation-based Riskscore model aids in patient stratification and treatment selection. HNRNPH1 regulates lactylation, thereby affecting patient prognosis.

BackgroundPrimary healthcare workers in China were vital in controlling COVID-19, facing unprecedented challenges due to the pandemic’s suddenness and transmissibility. This paper analyzed their work in Guangzhou, highlighting key difficulties in past epidemic control efforts.MethodsSemi-structured qualitative interviews were conducted with selected primary healthcare workers in Guangzhou City and audio-recorded until saturation of themes was reached. The data were analyzed independently for themes using NVivo V.12.ResultsThematic analysis of qualitative interview data revealed that challenges and difficulties encountered in grassroots epidemic prevention and control work during the COVID-19 pandemic were primarily categorized into seven dimensions: human resource allocation, material and vehicle support, epidemic prevention subsidies and compensation, humanistic care, upper-level management, horizontal collaboration, and resident cooperation.ConclusionBased on the findings, the research team recommends that administrative departments and institutions related to primary healthcare should appropriately schedule personnel work and rest time, adjust work content flexibly, optimize the allocation of medical and logistical resources, and increase investment in primary healthcare work as well as staff protection.

ABSTRACT Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = −0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = −0.4451) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = −0.3868) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

Abstract PTENα/β, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/β to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.

Abstract94% of Fortune 1000 firms experienced supply chain disruptions. The severe shortage of essential medical supplies caused by COVID-19 has severely hampered the healthcare supply chain (HCSC). This study explores the impact of supply chain resilience (SCR) on supply chain performance (SCP) and the impact of communication (COM), organization culture (OC), top management support (TMS), and product complexity (PC) on SCR. The establishment of a theoretical framework is the goal of this study. This paper adopts mixed research methodologies: the qualitative method using semi-structured interviews and NVivo data analysis, and the quantitative method based on self-administered questionnaires and SmartPLS analysis. The study investigated SCR in the Chinese healthcare industry from the perspective of CAS (complex adaptive systems). 32 Tier-4 healthcare organizations from China took part in the interviews. 162 businesses filled out questionnaires to gather data from Chinese healthcare suppliers or manufacturers. The results suggested that SCR positively impacts SCP, and COM, OC, and PC positively impact SCR, but empirical evidence for the significance of TMS on SCR is still lacking. Top management in China’s healthcare sector still needs to improve SCR management, especially by incorporating digital technology into the direction of the company’s supply chain, including supply chain innovation brought about by new technology and big data analysis. This study can be expanded to include Chinese healthcare. In response to supply chain disruptions, this effort will improve SCR.

Autism spectrum disorders (ASD) are associated with cognitive dysfunctions, including mental time travel (MTT). However, findings on diminished MTT ability may be confounded by a number of factors, including the individuals' language ability, factors related to the MTT task and the demographic factors of participants. The present study provided a meta-analysis of MTT ability in people with ASD. The results showed significant overall reductions in MTT ability in people with ASD. Moderator analyses revealed that the variables examined did not explain the reduction in MTT ability. These findings suggest that MTT ability is diminished in people with ASD and that the degree of this diminishment may not depend on the characteristics of measures or demographic variables of people with ASD.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

This paper investigates the chaotic synchronization of neural networks via sampled-data control with actuator saturation. First, a new generalized looped-functional is constructed by considering valid information from $t_{k}$ to t and from t to $t_{k+1}$ . Then, local stability conditions for the synchronization error system are given based on the Lyapunov stability theory. A sampled-data controller is designed to achieve the synchronization of the driving neural network and the response neural network by solving the convex optimization problem with given conditions. The proposed method’s effectiveness and practicality are numerically verified.