Neuregulin 1 mitigated prolactin deficiency through enhancing TRPM8 signaling under the influence of melatonin in senescent pituitary lactotrophs.

The age-related alterations in pituitary function, including changes in prolactin (PRL) production contributes to the systemic susceptibility to age-related diseases. Our previous research has shown the involvement of Nrg1 in regulating the expression and secretion of PRL. However, the precise role of Nrg1 in mitigating the senescence of pituitary lactotrophs and the underlying mechanisms are yet to be comprehended. Here, data from the GEPIA database was used to evaluate the association between transient receptor potential cation channel subfamily M member 8 (TRPM8) and PRL in normal human pituitary tissues, followed by immunofluorescence verification using a human pituitary tissue microarray. TRPM8 levels showed a significant positive association with PRL expression in normal human pituitary tissues, and both TRPM8 and PRL levels declined during aging, suggesting that TRPM8 may regulate pituitary aging by affecting PRL production. It was also found that treatment with exogenous neuregulin 1 (Nrg1) markedly delayed the senescence of GH3 cells (rat lactotroph cell line) generated by D-galactose (D-gal). In addition, melatonin reduced the levels of senescence-related markers in senescent pituitary cells by promoting Nrg1 / ErbB4 signaling, stimulating PRL expression and secretion. Further investigation showed that Nrg1 attenuated senescence in pituitary cells by increasing TRPM8 expression. Downregulation of TRPM8 activation eliminated Nrg1-mediated amelioration of pituitary cell senescence. These findings demonstrate the critical function of Nrg1 / ErbB signaling in delaying pituitary lactotroph cell senescence and enhancing PRL production via promoting TRPM8 expression under the modulation of melatonin.

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied. AIM: To investigate the relationship between NLR and renal function in T2DM patients. METHODS: This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center. The total number of neutrophils and lymphocytes was detected, and NLR levels were calculated. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m². Participants were divided into four groups based on NLR levels. The clinical data and biochemical characteristics were compared among groups. A multivariate logistic regression model was used to analyze the association between NLR levels and CKD. RESULTS: Significant differences were found in terms of sex, serum creatinine, blood urea nitrogen, total cholesterol, and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups (P < 0.0007). T2DM patients in the highest NLR quartile had a higher prevalence of CKD (P for trend = 0.0011). Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters (P = 0.0001, odds ratio = 1.41, 95% confidence intervals: 1.18-1.68). CONCLUSION: An elevated NLR in patients with T2DM is associated with higher prevalence of CKD, suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

Home care needs assessment among caregivers of children and adolescents with osteogenesis imperfecta: a cross-sectional study.

BACKGROUND: Children and adolescents with complex medical issues need home care services; however, few studies have provided insight into the unmet home care needs of the families of patients with osteogenesis imperfecta (OI). In this study, we aimed to assess the home care needs of caregivers of children and adolescents with OI and the associated factors. METHODS: A self-administered questionnaire was administered online to 142 caregivers of patients with OI aged 3-17 years between May and October 2022 from 25 provinces in China. The questionnaire comprised 15 questions on demographic variables and 14 questions on home care needs. Chi-square analysis was used to compare group differences for categorical variables. Multivariate binary logistic regression analysis was conducted to examine predictors of caregivers' home care needs. RESULTS: The study findings indicated that 81.5% of caregivers had high home care needs. The three leading types of home care needs were helping the child carry out physical fitness recovery exercises at home (72.5%), understanding precautions regarding treatment drugs (72.5%), and relieving the child's pain (70.4%). OI patients' poor self-care ability (adjusted odds ratio = 5.9, 95% confidence interval = 1.8-19.0) was related to caregivers' high level of home care needs. CONCLUSIONS: The findings of this study suggest that future scientific research and nursing guidance should focus on OI patients' physical training, medication management, pain relief, fracture prevention, and treatment. In addition, caregivers of patients with poor self-care ability should receive special attention in the development of interventions. This study can help with addressing the unmet home care needs of caregivers of children and adolescents with OI. It is vital to develop a personalized intervention plan based on patients' self-care ability.

Reducing polypyrimidine tract­binding protein 1 fails to promote neuronal transdifferentiation on HT22 and mouse astrocyte cells under physiological conditions.

In contrast to prior findings that have illustrated the conversion of non-neuronal cells into functional neurons through the specific targeting of polypyrimidine tract-binding protein 1 (PTBP1), accumulated evidence suggests the impracticality of inducing neuronal transdifferentiation through suppressing PTBP1 expression in pathological circumstances. Therefore, the present study explored the effect of knocking down PTBP1 under physiological conditions on the transdifferentiation of mouse hippocampal neuron HT22 cells and mouse astrocyte (MA) cells. A total of 20 µM negative control small interfering (si)RNA and siRNA targeting PTBP1 were transfected into HT22 and MA cells using Lipo8000™ for 3 and 5 days, respectively. The expression of early neuronal marker ßIII-Tubulin and mature neuronal markers NeuN and microtubule-associated protein 2 (MAP2) were detected using western blotting. In addition, ßIII-tubulin, NeuN and MAP2 were labeled with immunofluorescence staining to evaluate neuronal cell differentiation in response to PTBP1 downregulation. Under physiological conditions, no significant changes in the expression of ßIII-Tubulin, NeuN and MAP2 were found after 3 and 5 days of knockdown of PTBP1 protein in both HT22 and MA cells. In addition, the immunofluorescence staining results showed no apparent transdifferentiation in maker levels and morphology. The results suggested that the knockdown of PTBP1 failed to induce neuronal differentiation under physiological conditions.

14-3-3ζ targets ß-catenin nuclear translocation to maintain mitochondrial homeostasis and promote the balance between proliferation and apoptosis in cisplatin-induced acute kidney injury.

Cisplatin is a chemotherapeutic agent that is used extensively to treat solid tumors; however, its clinical application is limited by side effects, especially nephrotoxicity. Cisplatin-induced acute kidney injury (AKI) is characterized by DNA damage, cell-cycle arrest, and mitochondrial oxidative stress. Recent research demonstrated that 14-3-3ζ plays an important role in cancers, nerve disease, and kidney disease, although the regulatory mechanisms underlying cisplatin-induced AKI have yet to be fully elucidated. In the present study, we found that 14-3-3ζ mRNA was upregulated in human kidney organoids (GSE145085) when treated with cisplatin; subsequently, this was confirmed in experimental mice. The application of a protein interaction inhibitor for 14-3-3 (BV02) resulted in a decline in renal function, along with apoptosis, mitochondrial dysfunction, and oxidative stress in cisplatin-induced AKI. Accordingly, the knockdown of 14-3-3ζ in cisplatin-treated NRK-52E cells led to increased apoptosis, cell-cycle arrest, the production of reactive oxygen species (ROS), and lipid dysbolism. Furthermore, the blockade of 14-3-3ζ, both in vivo and in vitro, suppressed ß-catenin and its nuclear translocation, thus downregulating expression of the downstream gene cyclin D1 in cisplatin-induced damage. In contrast, the overexpression of 14-3-3ζ alleviated the injury caused by cisplatin both in vivo and in vitro. Furthermore, a non-specific agonist of ß-catenin, BIO, reversed the effects of 14-3-3ζ knockdown in terms of cisplatin-induced damage in NRK-52E cells by activating ß-catenin. Next, we verified the direct interaction between 14 - 3-3ζ and ß-catenin by CO-IP and immunofluorescence. Collectively, these findings indicate that 14-3-3ζ protects against cisplatin-induced AKI by improving mitochondrial function and the balance between proliferation and apoptosis by facilitating the nuclear translocation of ß-catenin.

Involvement of CXCL10 in Neuronal Damage under the Condition of Spinal Cord Injury and the Potential Therapeutic Effect of Nrg1.

OBJECTIVE: Few studies have reported the direct effect of C-X-C motif chemokine ligand 10 (CXCL10) and Neuregulin 1 (Nrg1) on neurons after spinal cord injury (SCI). This study reports the role of CXCL10 in the regulation of neuronal damage after SCI and the potential therapeutic effect of Nrg1. METHODS: The expression level of CXCL10 and Nrg1 in SCI mice was analyzed in the Gene Expression Omnibus DataSets, followed by immunohistochemical confirmation using a mouse SCI model. HT22 cells and NSC34 cells were treated with CXCL10 and Nrg1, individually or in combination, and then assayed for cell viability. The percentage of wound closure was determined through the cell scratch injury model using HT22 and NSC34 cells. Potential molecular mechanisms were also tested in response to either the individual administration of CXCL10 and Nrg1 or a mixture of both molecules. RESULTS: CXCL10 expression was significantly increased in both young and old mice subjected to SCI, while Nrg1 expression was significantly decreased. CXCL10 induced a decrease in cell viability, which was partially reversed by Nrg1. CXCL10 failed to inhibit scratch healing in HT22 and NSC34 cells, while Nrg1 promoted scratch healing. At the molecular level, CXCL10-activated cleaved caspase 9 and cleaved caspase 3 were both inhibited by Nrg1 through pERK1/2 signaling in HT22 and NSC34 cells. CONCLUSIONS: CXCL10 is upregulated in SCI. Despite the negative effect on cell viability, CXCL10 failed to inhibit the scratch healing of HT22 and NSC34 cells. Nrg1 may protect neurons by partially antagonizing the effect of CXCL10.

Association between gut microbial diversity and technique failure in peritoneal dialysis patients.

BACKGROUND: Gut dysbiosis in peritoneal dialysis (PD) patients causes chronic inflammation and metabolic disorders which result in a series of complications, probably playing an important role in PD technique failure. The reduction in gut microbial diversity was a common feature of gut dysbiosis. The objective was to explore the relationship between gut microbial diversity and technique failure in PD patients. METHODS: The gut microbiota was analyzed by 16s ribosomal RNA gene amplicon sequencing. Cox proportional hazards models were used to identify association between gut microbial diversity and technique failure in PD patients. RESULTS: In this study, a total of 101 PD patients were enrolled. During a median follow-up of 38 months, we found that lower diversity was independently associated with a higher risk of technique failure (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.319-5.456; p = 0.006). In addition, older age (HR, 1.034; 95% CI, 1.005-1.063; p = 0.020) and the history of diabetes (HR, 5.547; 95% CI, 2.218-13.876; p < 0.001) were also independent predictors for technique failure of PD patients. The prediction model constructed on the basis of three independent risk factors above performed well in predicting technique failure at 36 and 48 months (36 months: area under the curve [AUC] = 0.861; 95% CI, 0.836-0.886; 48 months: AUC = 0.815; 95% CI, 0.774-0.857). CONCLUSION: Gut microbial diversity was independently correlated with technique failure in PD patients, and some specific microbial taxa may serve as a potential therapeutic target for decreasing PD technique failure.

Diet therapy in patients with rare diseases: a scoping review.

BACKGROUND: This scoping review presents existing research evidence regarding diet therapy in patients with rare diseases (RDs). METHODS: Using the five-stage scoping review framework proposed by Arksey, O'Malley and Levac, we searched the published literature in PubMed, Web of Science, Royal Society of Chemistry, China National Knowledge Infrastructure, VIP Database and Wan Fang Database from January 2010 to November 2022. We selected diet therapy studies on 121 RDs, as categorised by the National Health Commission of China in 2018. Charts for research analysis were developed and used to categorise the data. RESULTS: We ultimately included 34 diet therapy studies from 19 countries and territories for 10 RDs and 3 RD groups. RD diet therapy studies have mainly focused on inborn errors of metabolism (92.3%) and are common in Western countries. Most studies focused on diet therapy methods for RDs (44%). In addition, 29% of studies included diet therapy management, 15% included guidelines for diet therapy and 12% included the impact of diet therapy on patients. CONCLUSIONS: Current diet therapies for RDs lack specificity and present with limited characteristics. Therefore, it is necessary to expand the scope and depth of future research and explore evidence-based recommendations and new diet therapies focused on patient needs and family support to provide a reference for improving the efficacy and safety of diet therapies for RDs.

Experiences of COVID-19 patients in a Fangcang shelter hospital in China during the first wave of the COVID-19 pandemic: a qualitative descriptive study.

OBJECTIVES: This study aimed to examine COVID-19 patients' experiences in a Fangcang shelter hospital in China, to provide insights into the effectiveness of this centralised isolation strategy as a novel solution to patient management during emerging infectious disease outbreaks. DESIGN: This study adopted a qualitative descriptive design. Data were collected by individual semistructured interviews and analysed using thematic analysis. SETTING: This study was undertaken in 1 of the 16 Fangcang shelter hospitals in Wuhan, China between 28 February 2020 and 7 March 2020. Fangcang shelter hospitals were temporary healthcare facilities intended for large-scale centralised isolation, treatment and disease monitoring of mild-to-moderate COVID-19 cases. These hospitals were an essential component of China's response to the first wave of the COVID-19 pandemic. PARTICIPANTS: A total of 27 COVID-19 patients were recruited by purposive sampling. Eligible participants were (1) COVID-19 patients; (2) above 18 years of age and (3) able to communicate effectively. Exclusion criteria were (1) being clinically or emotionally unstable and (2) experiencing communication difficulties. RESULTS: Three themes and nine subthemes were identified. First, COVID-19 patients experienced a range of psychological reactions during hospitalisation, including fear, uncertainty, helplessness and concerns. Second, there were positive and negative experiences associated with communal living. While COVID-19 patients' evaluation of essential services in the hospital was overall positive, privacy and hygiene issues were highlighted as stressors during their hospital stay. Third, positive peer support and a trusting patient-healthcare professional relationship served as a birthplace for resilience, trust and gratitude in COVID-19 patients. CONCLUSIONS: Our findings suggest that, while sacrificing privacy, centralised isolation has the potential to mitigate negative psychological impacts of social isolation in COVID-19 patients by promoting meaningful peer connections, companionship and support within the shared living space. To our knowledge, this is the first study bringing patients' perspectives into healthcare service appraisal in emergency shelter hospitals.

Relationship between knowledge, attitudes, and practices and COVID-19 vaccine hesitancy: A cross-sectional study in Taizhou, China.

Objective: This study aimed to explore COVID-19 vaccine hesitancy in Chinese adults and analyzed the relationship between knowledge, attitudes, practices (KAP), and COVID-19 vaccine hesitancy. Methods: A population-based self-administered online survey was conducted in Taizhou, China to evaluate the population's hesitancy to receive COVID-19 vaccination. A total of 2.463 adults received the invitation for the survey through WeChat (A Chinese app that is used for chat, social media, and mobile payment), and 1.788 interviewees answered the structured questionnaire. The overall response rate was 72.6%. Results: Total 45.2% of people were hesitant about the COVID-19 vaccination. Using binary logistic regression analysis, we found low perception of safety (Model 3: Odds ratio = 2.977, Confidence interval: 2.237-3.963) and efficacy (Model 3: OR = 1.904, 95%CI: 1.462-2.479) of the COVID-19 vaccine in adults is the most important risk factor for COVID-19 vaccine hesitation. People who know more about COVID-19 vaccination are less hesitant (Model 2: OR = 0.967, 95% CI: 0.951-0.983). People who did not seek information independently about the COVID-19 vaccine are more likely to be skeptical (Model 4: OR = 1.300, 95% CI: 1.058-1.598, P = 0.013). Conclusion: In China, the population had higher levels of COVID-19 vaccine hesitation, and their knowledge of the COVID-19 vaccine, perceptions of safety and efficacy, and physical health status were significantly associated with vaccine hesitation. These results provide ideas for promoting COVID-19 vaccination and intervention and have far-reaching implications for further strengthening research on vaccine hesitancy in COVID-19 and exploring strategies for COVID-19 vaccine promotion.

[Analysis of Pollution Characteristics and Sources of Rainfall Runoff from Roofs in the Central District of Beijing].

The rainwater and rainfall runoff of roofs in the central district of Beijing from June to September in 2019 were sampled and analyzed to study the characteristics of the water quality, the first flush effect, and the main influential factors and sources of pollutants. The results showed that the roof runoff was seriously polluted by total nitrogen, ammonia nitrogen, chemical oxygen demand, and total suspended solids whose event mean concentration (EMC) exceeded the fifth level of environmental quality standards for surface water (GB 3838-2002) (the EMC of suspended solids exceeded the second level of discharge standard of pollutants for municipal wastewater treatment plants (GB 18918-2002)). The rainwater was relatively less polluted than the rainfall runoff, but the EMC of ammonia nitrogen and total nitrogen of the rainwater also exceeded the standard in some rainfall events. The first flush intensity of the rainfall runoffs was between weak and medium. The sequence of strength of the first flush of different pollutants was ammonia nitrogen>total suspended solids>chemical oxygen demand>total nitrogen>mercury>zinc>total phosphorus>lead. The concentration of total suspended solids, chemical oxygen demand, and total phosphorus in roof runoff were significantly positively correlated with the length of rainfall and the dry period and negatively correlated with the rainfall intensity. According to the results of principal component analysis, the main pollutant in rainwater was nitrogen emitted by vehicles, and the main pollutants in roof runoffs were suspended solids, organic matters, and phosphorus pollutants released from the aging of roofing materials and the corrosion of metal down pipes.

Nanotechnology in Kidney and Islet Transplantation: An Ongoing, Promising Field.

Organ transplantation has evolved rapidly in recent years as a reliable option for patients with end-stage organ failure. However, organ shortage, surgical risks, acute and chronic rejection reactions and long-term immunosuppressive drug applications and their inevitable side effects remain extremely challenging problems. The application of nanotechnology in medicine has proven highly successful and has unique advantages for diagnosing and treating diseases compared to conventional methods. The combination of nanotechnology and transplantation brings a new direction of thinking to transplantation medicine. In this article, we provide an overview of the application and progress of nanotechnology in kidney and islet transplantation, including nanotechnology for renal pre-transplantation preservation, artificial biological islets, organ imaging and drug delivery.

Using the theory of planned behaviour to explain junior nurses' and final-year student nurses' intention to care for COVID-19 patients in China: A multisite cross-sectional study.

AIM: To explore junior nurses' and final-year student nurses' intention to care for COVID-19 patients amidst the Delta COVID-19 variant outbreak in China using the theory of planned behaviour (TPB) as a framework. BACKGROUND: The COVID-19 pandemic has intensified global nursing shortage. Junior nurses and final-year student nurses represent the backbone of the future frontline nursing workforce. The TPB is a valid theoretical model for predicting nurses' caring behaviours. METHODS: A 47-item self-administered questionnaire was disseminated online to a convenience sample of 547 junior nurses and final-year student nurses located in 13 regions across mainland China. RESULTS: Approximately 63.4% of the participants intended to care for COVID-19 patients voluntarily and 65.6% by non-voluntary assignment. The TPB model significantly predicted 45% of the variance in behavioural intention, subjective norms being the strongest predictor. Gender, vaccination status and ethical perceptions regarding frontline work significantly correlated with the intention to provide care. CONCLUSIONS: Our findings highlight the importance of social, organisational and family support underpinning future junior nurses' professional commitment in times of public health crisis. IMPLICATIONS FOR NURSING MANAGEMENT: Pandemic-tailored workplace training programmes for nurses/student nurses that emphasize on self-care and ethical issue discussions are warranted. Hospital managers should collaborate with community partners to offer additional family support for nurses in need.

Monodispersed silver-gold nanorods controllable etching for ultrasensitive SERS detection of hydrogen peroxide-involved metabolites.

Hydrogen peroxide (H2O2)-involved metabolites are widely engaged in cellular metabolism, and play significant roles in cell proliferation, cell growth, and signaling transduction. It is highly desirable to establish a method for the detection of H2O2-involved metabolites for applications ranging from chemical sensing to biomedical diagnosis. Herein, monodispersed sandwich Au@4-MBN@Ag@PEG nanorods (referred to as AMPRs) with bright Raman emission were developed to serve as a universal platform for detecting H2O2-involved metabolites (4-mercaptobenzonitrile is abbreviated to 4-MBN as the Raman reporter and PEG is polyethylene glycol). The system detects metabolites through changes in the surface-enhanced Raman scattering (SERS) spectrum, resulting from the controllable etching of the silver layer by the H2O2 produced by the metabolites. The integrative nanoplatform was successfully used to quantify the levels of glucose, lactate, and choline in aqueous solutions by exploiting the close linear relationship between the intensity of a SERS band and the logarithmic concentration of H2O2. The presented SERS nanoplatform demonstrated considerable practicability for the detection of glucose in cerebrospinal fluid samples (with a limit of detection (LOD) of 1.76 µM), and was capable of distinguishing infected from uninfected individuals. Therefore, the SERS sensor provides a new platform for the detection of H2O2-involved metabolites in biological fluids, and has potential for use in metabolite analysis and biomedical diagnostics.

Sublethal Exposure to Deltamethrin Stimulates Reproduction and Alters Symbiotic Bacteria in Aphis gossypii.

In aphids, hormesis and symbiotic bacteria are the drivers for the development of pesticide resistance. However, the related mechanism remains unclear. Here, we evaluated the sublethal and transgenerational effects of the extensively used pyrethroid pesticide deltamethrin (DMT) on the population dynamics in Aphis gossypii and tested its influence on symbiotic bacterial communities. The leaf-dip bioassay revealed that DMT was highly toxic to A. gossypii, and at a low lethal concentration of DMT, the intrinsic (r) and finite rates of increase (λ) of the initially exposed aphids (G0) significantly decreased. Intriguingly, the r, λ, and net reproductive rate (R0) of G1 and G2 significantly increased, but the r and λ decreased in G3. The adult and total preoviposition period increased in G3 but decreased in G4. Additionally, the diversity of the bacterial community decreased, while the abundance values of Buchnera, Pseudomonadaceae, and Burkholderiaceae increased after 24 h of exposure to LC30 DMT in G0 aphids, and the latter two decreased in G1 but increased in G2. In summary, sublethal DMT has intergenerational hormesis effect on cotton aphids in G1-G2 and remarkably altered their symbiotic bacterial community and abundance. These results broaden our understanding of the relationship of hormesis and symbiotic bacteria in aphids under insecticide exposure.

Iodide-modified Ag nanoparticles coupled with DSN-Assisted cycling amplification for label-free and ultrasensitive SERS detection of MicroRNA-21.

With the emergence of microRNA (miRNA) as a key player in early clinical disease diagnosis, development of rapidly sensitive and quantitative miRNA detection methods are imperative. Herein, a label-free SERS assay coupled with duplex-specific nuclease (DSN) signal amplification strategy was proposed for facilely ultrasensitive and quantitative analysis of miRNA-21. Firstly, magnetic beads assembled with excessive capture DNA were utilized to hybridize the target miRNA-21. These DNA-RNA heteroduplexes were cleaved by DSN to generate small nucleotide fragments into the supernatant and the miRNA-21 released and rehybridized another DNA, going to the next DSN cycle. Consequently, numerous of small nucleotide fragments of capture DNA were released from magnetic beads and the miRNA-21 signal was transferred and amplified by the SERS signals of total phosphate backbones which are abundant in nucleotide. Furthermore, iodide-modified Ag nanoparticles (AgINPs) was employed to generate a strong and reproducible SERS signal. The proposed method displayed excellent performance for miRNA-21 detection with the linear range from 0.33 fM to 3.3 pM, and a lower detection limit of 42 aM. Moreover, this strategy exhibited effectively base discrimination capability and was successfully applied for monitoring the expression levels of miRNA-21 in different cancer cell lines and human serum.

PD-1-Positive Tumor-Associated Macrophages Define Poor Clinical Outcomes in Patients With Muscle Invasive Bladder Cancer Through Potential CD68/PD-1 Complex Interactions.

Tumor-associated macrophages (TAMs) regulate tumor immunity. Previous studies have shown that the programmed cell death protein 1 (PD-1)-positive TAMs have an M2 macrophage phenotype. CD68 is a biomarker of TAMs and is considered to be a poor prognostic marker of several malignancies. Our results show that PD-1-positive TAMs can be a negative survival indicator in patients with muscle-invasive bladder cancer (MIBC), and that the mechanistic effects could result due to a combination of PD-1 and CD68 activity. We analyzed 22 immune cell types using data from 402 patients with MIBC from the TCGA database, and found that a high immune score and M2 TAMs were strongly associated with poor clinical outcomes in patients with MIBC. Further, we analyzed resected samples from 120 patients with MIBC and found that individuals with PD-1-positive TAMs showed a reduction in 5-year overall survival and disease-free survival. Additionally, PD-1-positive TAMs showed a significant association with higher programmed death-ligand 1 (PD-L1) expression, the Ki67 index, the pT stage and fewer CD8-positive T cells. Through the co-immunoprecipitation (co-IP) assay of THP-1 derived macrophages, we found that CD68 can bind to PD-1. The binding of CD68 and PD-1 can induce M2 polarization of THP-1 derived macrophages and promote cancer growth. The anti-CD68 treatment combined with peripheral blood mononuclear cells (PBMC) showed obvious synergy effects on inhibiting the proliferation of T24 cells. Together, these results indicate for the first time that CD68/PD-1 may be a novel target for the prognosis of patients with MIBC.

Characterization of four mitochondrial genomes of family Neritidae (Gastropoda: Neritimorpha) and insight into its phylogenetic relationships.

Neritidae is one of the most diverse families of Neritimorpha and possesses euryhaline properties. Members of this family usually live on tropical and subtropical coasts and are mainly gregarious. The phylogenetic relationships between several subclasses of Gastropoda have been controversial for many years. With an increase in the number of described species of Neritidae, the knowledge of the evolutionary relationships in this family has improved. In the present study, we sequenced four complete mitochondrial genomes from two genera (Clithon and Nerita) and compared them with available complete mitochondrial genomes of Neritidae. Gene order exhibited a highly conserved pattern among three genera in the Neritidae family. Our results improved the phylogenetic resolution within Neritidae, and more comprehensive taxonomic sampling of subclass Neritimorpha was proposed. Furthermore, we reconstructed the divergence among the main lineages of 19 Neritimorpha taxa under an uncorrelated relaxed molecular clock.

Evaluation of sublethal and transgenerational effects of sulfoxaflor on Aphis gossypii via life table parameters and 16S rRNA sequencing.

BACKGROUND: Aphis gossypii, a polyphagous and recurrent pest induced by pesticides, causes tremendous loss crop yields each year. Previous studies on the mechanism of pesticide-induced sublethal effects mainly focus on the gene level. The symbiotic bacteria are also important participants of this mechanism, but their roles in hormesis are still unclear. RESULTS: In this study, life table parameters and 16S rRNA sequencing were applied to evaluate the sublethal and transgenerational effects of sulfoxaflor on adult A. gossypii after 24-h LC20 (6.96 mg L-1 ) concentration exposure. The results indicated that the LC20 of sulfoxaflor significantly reduced the finite rate of increase (λ) and net reproductive rate (R0 ) of parent generation (G0), and significantly increased mean generation time (T) of G1 and G2, but not of G3 and G4. Both reproductive period and fecundity of G1 and G2 were significantly higher than those of the control. Furthermore, our sequencing data revealed that more than 95% bacterial communities were dominated by the phylum Proteobacteria, in which the maximum proportion genus was the primary symbiont Buchnera and the facultative symbiont Arsenophonus. Compared to those of the control, the abundance and composition of symbiotic bacteria of A. gossypii for three successive generations (G0-G2) were changed after G0 A. gossypii was exposed to sulfoxaflor: the diversity of the bacterial community was decreased, but the abundance of Buchnera was increased (G0), while the abundance of Arsenophonus was decreased. Contrary to G0, G1 and G2 cotton aphid exhibited an increased relative abundance of Arsenophonus in the sublethal treatment group. CONCLUSION: Taken together, our results provide an insight into the interactions among pesticide resistance, aphids, and symbionts, which will eventually help to better manage the resurgence of A. gossypii. © 2021 Society of Chemical Industry.

Preparation of PEG-modified wool keratin/sodium alginate porous scaffolds with elasticity recovery and good biocompatibility.

To improve mechanical properties of keratin (KR) porous scaffolds, we prepared a PEGylated keratin through thiol-ene click reaction. Several porous scaffolds were prepared by blending PEGylated keratin with sodium alginate (SA). The surface morphology, mechanical properties, and porosity of scaffolds were detailed studied at different KR/SA proportions. The results showed the content of SA had an effect on pore formation and mechanical properties. When the mass ratio of KR to SA was 2:1, the stress of yield point of the keratin porous scaffold reached 1.24 MPa, and also showed good deformation recovery ability. The PEGylated keratin porous scaffold had a high porosity and great cytocompatibility. Its' porosity is up to 81.7% and the cell viability is about 117.78%. This allows it to absorb the simulated plasma quickly (9.20 ± 0.37 g/g). In addition, the structural stability and acid-base stability of the keratin porous scaffold were also improved after PEGylation. Overall, the PEGylated keratin porous scaffold will be promising in tissue materials due to its great physical, chemical, and biological properties.