Enhanced methane production from waste activated sludge by microbial electrolysis cell assisted anaerobic digestion: Fate and effect of humic substances.

Humic substances as major components of waste activated sludge are refractory to degrade and have inhibition in traditional anaerobic digestion (AD). This study for the first time investigated the feasibility and mechanism of microbial electrolysis cell assisted anaerobic digestion (MEC-AD) to break the recalcitrance and inhibition of humic substances. The cumulative methane production of AD decreased from 134.7 to 117.6 mL/g-VS with the addition of humic acids and fulvic acids at 25.2-102.1 mg/g-VS. However, 0.6 V MEC-AD maintained stable methane production (155.5-158.2mL/g-VS) under the effect of humic substances. 0.6 V MEC-AD formed electrical stimulation on microbial cells, provided anodic oxidation and cathodic reduction transformation pathways for humic substances (acting as carbon sources and electron shuttles), and aggregated functional microorganisms on electrodes, facilitating the degradation of humic substances and generation of methane. This study provides a theoretical basis for improving the energy recovery and system stability of sludge treatment.

Effect of Regular Aerobic Exercise on Cognitive Function, Depression Level and Regulative Role of Neurotrophic Factor: A Prospective Cohort Study in the Young and the Middle-Aged Sample.

Purpose: Mild cognitive impairment (MCI) and depressive disorder (DD), which are associated with unhealthy lifestyles, are prevalent worldwide. This study aimed to investigate the effects of regular aerobic exercise on cognitive function, depression, and the regulatory role of neurotrophic growth factors for providing scientific basis in preventing MCI and DD in healthy individuals. Patients and Methods: Eighty members of the fitness center and 80 community residents were recruited, who were administered by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Patient Health Questionnaire (PHQ-9). Brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) in the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Results: The RBANS and other factor scores, except for visuospatial abilities, were higher and PHQ-9 scores were lower in the study group than in the control group. The concentrations of BDNF and GDNF in the study group were higher than those in the control group. RBANS and its factor scores positively and PHQ-9 negatively correlated with BDNF and GDNF levels. Finally, multiple regression analysis showed that BDNF, as a predictor of RBANS, could explain 59.90% of its variance and that GDNF was a predictor of PHQ-9 could explain 12.30% of the variance. Conclusion: Regular aerobic exercise can improve cognitive function and depressive symptoms by increasing the BDNF and GDNF levels.

Liproxstatin-1 Alleviated Ischemia/Reperfusion-Induced Acute Kidney Injury via Inhibiting Ferroptosis.

Ferroptosis, as a novel regulable cell death, is characterized by iron overload, glutathione depletion, and an accumulation of lipid peroxides. Recently, it has been discovered that ferroptosis is involved in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and plays a crucial role in renal tubular cell death. In this study, we tried to investigate the effect and mechanism of liproxstatin-1 (Lip-1) in I/R-induced AKI and seek the key regulator of ferroptosis in I/R-induced AKI. Mice were administrated with clamping bilateral renal pedicles for 30 min. We found that early growth response 1 (EGR1) might be a key regulator of ferroptosis, and Lip-1 could suppress ferroptosis via EGR1. Meanwhile, Lip-1 could reduce macrophage recruitment and the release of inflammatory cytokines. These findings indicated that Lip-1 alleviated I/R-induced AKI via regulating EGR1, and it might pave the theoretical basis of a new therapeutic strategy for I/R-induced AKI.

Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Marked variations in diversity and functions of gut microbiota between wild and domestic stag beetle Dorcus Hopei Hopei.

BACKGROUND: Although stag beetles are a popular saprophytic insect, their gut microbiome has been poorly studied. Here, 16 S rRNA gene sequencing was employed to reveal the gut microbiota composition and functional variations between wild and domestic Dorcus hopei hopei (Dhh) larval individuals. RESULTS: The results indicated a significant difference between the wild and domestic Dhh gut microbiota., the domestic Dhh individuals contained more gut microbial taxa (e.g. genera Ralstonia and Methyloversatilis) with xenobiotic degrading functions. The wild Dhh possesses gut microbiota compositions (e.g. Turicibacter and Tyzzerella ) more appropriate for energy metabolism and potential growth. This study furthermore assigned all Dhh individuals by size into groups for data analysis; which indicated limited disparities between the gut microbiota of different-sized D. hopei hopei larvae. CONCLUSION: The outcome of this study illustrated that there exists a significant discrepancy in gut microbiota composition between wild and domestic Dhh larvae. In addition, the assemblage of gut microbiome in Dhh was primarily attributed to environmental influences instead of individual differences such as developmental potential or size. These findings will provide a valuable theoretical foundation for the protection of wild saprophytic insects and the potential utilization of the insect-associated intestinal microbiome in the future.

Noctiluca scintillans bloom alters the composition and carbohydrate utilization of associated bacterial community and enriches potential pathogenic bacterium Vibrio anguillarum.

Noctiluca scintillans (red) is a widely distributed heterotrophic dinoflagellate and a prominent red tide forming species. This study investigated the effects of Noctiluca blooms on marine microbial diversity and functionality using multi-omics approaches. Our findings revealed significant differences in the community composition of Noctiluca-associated bacteria compared to those associated with autotrophic plankton and free-living bacteria in the surrounding seawater. The dominant bacterial groups within the Noctiluca-associated community shifted at various bloom stages, which could be attributed to changes in prey composition of Noctiluca. During the non-bloom stage, Burkholderiaceae, Carnobacteriaceae, and Pseudomonadaceae dominated the community, while Vibrionaceae became dominant during the bloom stage, and Saprospiraceae, Crocinitomicaceae, and Pirellulaceae thrived during the post-bloom stage. Compared to the non-bloom stage, Noctiluca-associated bacterial community at the bloom stage exhibited significant down-regulation of genes related to complex carbohydrate metabolism, while up-regulation of genes related to glucose transportation and utilization. Furthermore, we identified Vibrio anguillarum, a potential pathogenic bacterium to marine fish, as a major component of the Vibrionaceae family during the bloom stage. The occurrence of V. anguillarum associated with Noctiluca blooms may be attributed to the increased availability of its preferred carbon sources and its high capabilities in glucose transportation, motility and chemotaxis. Moreover, the presence of Vibrio infection genes (hap, hlyA, rtxA) encoding vibriolysin, hemolysin, and RTX (Repeats-in-toxin) toxin in the V. anguillarum genome, with the hap gene showing high expression levels during Noctiluca blooms, indicates an elevated risk of infection. This study underscores the unique composition of the bacterial community associated with red tide forming heterotrophic dinoflagellates and suggests that Noctiluca cells may serve as reservoirs and vectors for pathogenic bacteria, potentially posing a threat to fish-farming and the health of other marine organisms.

Anchoring flap suture technique to repair a wound with exposed bone after hip disarticulation: a case report and brief review of the literature.

BACKGROUND: In specific clinical scenarios characterized by poor tissue conditions surrounding a wound, achieving stable flap fixation with standard sutures can be challenging. The anchoring flap suture technique, which is commonly used for soft tissue-to-bone attachment in cases of injury, may be an alternative and effective approach. CASE REPORT: This report describes the successful application of the anchoring flap suture technique to repair a wound with exposed bone in a 39-year-old female patient. She presented with a 7% TBSA wound of the left trunk following hip disarticulation. After 4 operations, a wound with exposed iliac bone remained. Given the compromised condition of the tissues surrounding the exposed bone, the authors opted to anchor a local flap directly to the exposed bone. Steady flap fixation was achieved using the anchoring flap suture method, resulting in complete healing of that wound. Remarkably, no short- or long-term complications associated with the flap were observed. Three months after hospital discharge, the patient regained mobility, walking on 1 leg with the assistance of a 4-legged walker. CONCLUSION: The anchoring flap suture technique seems to be a reliable and effective treatment option, particularly in cases in which inadequate soft tissue precludes the use of traditional flap fixation using standard sutures.

The Epidemiological Analysis of COVID-19 Outbreaks in Nursing Homes during the Period of Omicron Variant Predominance.

BACKGROUND: The main purpose of this study was to evaluate the epidemic trend and risk factors associated with COVID-19 outbreaks in nursing homes during the period of Omicron variant predominance. METHODS: The study analyzed the risk factors associated with SARS-CoV-2 infection and death among the 327 residents and 129 healthcare workers (HCWs) in three hospital-affiliated nursing homes through a multivariate Cox regression model. RESULTS: The rates of receiving a COVID-19 booster dose were 70.3% for the residents and 93.0% for the healthcare workers (HCWs), respectively. A number of asymptomatic individuals, including 54 (16.5%) residents and 15 (11.6%) HCWs, were detected through mass screening surveillance tests. The COVID-19 infection rates during the outbreaks were 41.6% among residents and 48.1% among HCWs, respectively. The case fatality rate among residents was 10.3%. None of the HCWs were hospitalized or died. The multivariate Cox regression model showed that the risk of COVID-19 infection increased in males (HR 2.46; 95% CI 1.47-4.11; p = 0.001), Barthel index ≥ 61 (HR 1.93; 95% CI 1.18-3.17; p = 0.009), and dementia (HR 1.61; 95% CI 1.14-2.27; p = 0.007). The risk of COVID-19 death increased with pneumonia (HR 11.03; 95% CI 3.02-40.31; p < 0.001), hospitalization (HR 7.18; 95% CI 1.97-26.25; p = 0.003), and admission to an intensive care unit (HR 8.67; 95% CI 2.79-26.89; p < 0.001). CONCLUSIONS: This study highlighted the high infection rates with a substantial proportion of asymptomatic infections for both residents and HCWs, as well as a high case fatality rate for the residents among nursing homes during the Omicron epidemic period. We suggest implementing mass screening through regular surveillance testing as an effective strategy for early detection of COVID-19 and for preventing transmission during an epidemic period. Pneumonia is the primary risk associated with COVID-19 death. Early detection and prompt treatment of pneumonia for vulnerable residents in nursing homes are crucial to protect them from potential mortality.

Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development.

The mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populations within tumors rather than tumor stem cells. Consequently, after a brief period of remission, tumors often relapse. Moreover, the exclusive targeting of tumor stemness cell disregards the potential for other tumor cells to regain stemness and acquire drug resistance. As a result, current drugs that solely target the HGF/c-MET axis and the Hh pathway demonstrate only moderate efficacy in specific types of cancer. Mounting evidence indicates that these two pathways not only play important roles in cancer but also exert significant influence on the development of resistance to single-target therapies through the secretion of their own ligands. In this comprehensive review, we analyze and compare the potential impact of the Hh pathway on the tumor microenvironment (TME) in HGF/c-MET-driven tumor models, as well as the interplay between different cell types. Additionally, we further substantiate the potential and necessity of dual-pathway combination therapy as a critical target in MET addicted cancer treatment. Video Abstract.

Ferroptosis: An Emerging Target for Bladder Cancer Therapy.

Bladder cancer (BC), as one of the main urological cancers in the world, possesses the abilities of multiple-drug resistance and metastasis. However, there remains a significant gap in the understanding and advancement of prognosis and therapeutic strategies for BC. Ferroptosis, a novel type of iron-dependent regulated cell death, depends on lipid peroxidation, which has been proven to have a strong correlation with the development and treatment of BC. Its mechanism mainly includes three pathways, namely, lipid peroxidation, the antioxidant system, and the iron overload pathway. In this review, we reviewed the mechanism of ferroptosis, along with the related therapeutic targets and drugs for BC, as it might become a new anticancer treatment in the future.

Branched-chain keto-acid dehydrogenase kinase regulates vascular permeability and angiogenesis to facilitate tumor metastasis in renal cell carcinoma.

Branched-chain keto-acid dehydrogenase kinase (BCKDK) is the rate-limiting enzyme of branched-chain amino acid (BCAA) metabolism. In the last six years, BCKDK has been used as a kinase to promote tumor proliferation and metastasis. Renal cell carcinoma (RCC) is a highly vascularized tumor. A high degree of vascularization promotes tumor metastasis. Our objective is to explore the relationship between BCKDK and RCC metastasis and its specific mechanism. In our study, BCKDK is highly expressed in renal clear cell carcinoma and promotes the migration of clear cell renal cell carcinoma (ccRCC). Exosomes from ccRCC cells can promote vascular permeability and angiogenesis, especially when BCKDK is overexpressed in ccRCC cells. BCKDK can also augment the miR-125a-5p expression in ccRCC cells and derived exosomes, thereby decreasing the downstream target protein VE-cadherin level, weakening adhesion junction expression, increasing vascular permeability, and promoting angiogenesis in HUVECs. The novel BCKDK/Exosome-miR-125a-5p/VE-cadherin axis regulates intercellular communication between ccRCC cells and HUVECs. BCKDK plays a critical role in renal cancer metastasis, may be used as a molecular marker of metastatic ccRCC, and even may become a potential target of clinical anti-vascular therapy for ccRCC.

TOPK mediates immune evasion of renal cell carcinoma via upregulating the expression of PD-L1.

Although anti-PD-L1 therapy has been used in the clinical treatment of renal cell carcinoma (RCC), a proportion of patients are not sensitive to it, which may be attributed to the heterogeneity of PD-L1 expression. Here, we demonstrated that high TOPK (T-LAK cell-originated Protein Kinase) expression in RCC promoted PD-L1 expression by activating ERK2 and TGF-ß/Smad pathways. TOPK was positively correlated with PD-L1 expression levels in RCC. Meanwhile, TOPK significantly inhibited the infiltration and function of CD8+ T cells and promoted the immune escape of RCC. Moreover, inhibition of TOPK significantly enhanced CD8+ T cell infiltration, promoted CD8+ T cell activation, enhanced anti-PD-L1 therapeutic efficacy, and synergistically enhanced anti-RCC immune response. In conclusion, this study proposes a new PD-L1 regulatory mechanism that is expected to improve the effectiveness of immunotherapy for RCC.

Comprehensive analysis of the prognosis and immune infiltration of TMC family members in renal clear cell carcinoma.

Renal cancer is a common malignancy of the urinary system, and renal clear cell carcinoma (RCCC) is the most common pathological type. Transmembrane channel-like (TMC) protein is an evolutionarily conserved gene family containing 8 members, however there is still a lack of comprehensive analysis about TMC family members in RCCC. In this study, we analyzed the expression of TMC family members in RCCC from TCGA and investigated the prognosis values and immune infiltration of TMC family members in RCCC. We found that TMC2, TMC3, TMC5, TMC7 and TMC8 were significantly related with overall survival (OS) of RCCC patients. TMC3, TMC6, and TMC8 was positively correlated with the degree of immune infiltration in RCCC. TMC2, TMC6, TMC7, and TMC8 were positively correlated with immune checkpoint genes, whereas TMC4 was negative. According to KEGG and GO analysis, almost all TMCs except TMC4 were involved in the immune response. Thus, we may regard the TMC family members as novel biomarkers to predict potential prognosis and immunotherapeutic response in RCCC patients.

BCKDK regulates breast cancer cell adhesion and tumor metastasis by inhibiting TRIM21 ubiquitinate talin1.

Breast cancer is the most common malignant cancer in women worldwide. Cancer metastasis is the major cause of cancer-related deaths. BCKDK is associated with various diseases, including proliferation, migration, and invasion in multiple types of human cancers. However, the relevance of BCKDK to the development and progression of breast cancers and its function is unclear. This study found that BCKDK was overexpressed in breast cancer, associated with poor prognosis, and implicated in tumor metastasis. The downregulation of BCKDK expression inhibited the migration of human breast cancer cells in vitro and diminished lung metastasis in vivo. BCKDK perturbed the cadherin-catenin complex at the adherens junctions (AJs) and assembled focal adhesions (FAs) onto the extracellular matrix, thereby promoting the directed migration of breast cancer cells. We observed that BCKDK acted as a conserved regulator of the ubiquitination of cytoskeletal protein talin1 and the activation of the FAK/MAPK pathway. Further studies revealed that BCKDK inhibited the binding of talin1 to E3 ubiquitin ligase-TRIM21, leading to the decreased ubiquitination/degradation of talin1. In conclusion, identifying BCKDK as a biomarker for breast cancer metastasis facilitated further research on diagnostic biomarkers. Elucidating the mechanism by which BCKDK exerted its biological effect could provide a new theoretical basis for developing new markers for breast cancer metastasis and contribute to developing new therapies for the clinical treatment of breast cancer patients.

Establishment and validation of a novel anoikis-related prognostic signature of clear cell renal cell carcinoma.

Background: Despite progression in its treatment, the clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) remains not ideal. Anoikis is a unique form of programmed apoptosis, owing to insufficient cell-matrix interactions. Anoikis plays a crucial role in tumor migration and invasion, and tumor cells could protect themselves through the capacity of anoikis resistance. Methods: Anoikis-related genes (ARGs) were obtained from Genecards and Harmonizome portals. The ARGs related to ccRCC prognosis were identified through univariate Cox regression analysis, then we utilized these ARGs to construct a novel prognostic model for ccRCC patients. Moreover, we explored the expression profile of ARGs in ccRCC using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. We also conducted Real-Time Polymerase Chain Reaction (RT-PCR) to probe ARGs expression of the risk score. Finally, we performed correlation analysis between ARGs and tumor immune microenvironment. Results: We identified 17 ARGs associated with ccRCC survival, from which 7 genes were chosen to construct a prognostic model. The prognostic model was verified as an independent prognostic indicator. The expression of most ARGs was higher in ccRCC samples. These ARGs were closely correlated with immune cell infiltration and immune checkpoint members, and had independent prognostic value respectively. Functional enrichment analysis demonstrated that these ARGs were significantly associated with multiple types of malignances. Conclusion: The prognostic signature was identified to be highly efficient in predicting ccRCC prognosis, and these ARGs were closely related to tumor microenvironment.

Boosting Cycling Stability of Polymer Sodium Battery by "Rigid-Flexible" Coupled Interfacial Stress Modulation.

The discontinuous interfacial contact of solid-state polymer metal batteries is due to the stress changes in the electrode structure during cycling, resulting in poor ion transport. Herein, a rigid-flexible coupled interface stress modulation strategy is developed to solve the above issues, which is to design a rigid cathode with enhanced solid-solution behavior to guide the uniform distribution of ions and electric field. Meanwhile, the polymer components are optimized to build an organic-inorganic blended flexible interfacial film to relieve the change of interfacial stress and ensure rapid ion transmission. The fabricated battery comprising a Co-modulated P2-type layered cathode (Na0.67Mn2/3Co1/3O2) and a high ion conductive polymer could deliver good cycling stability without distinct capacity fading (72.8 mAh g-1 over 350 cycles at 1 C), outperforming those without Co modulation or interfacial film construction. This work demonstrates a promising rigid-flexible coupled interfacial stress modulation strategy for polymer-metal batteries with excellent cycling stability.

[Effectiveness of new Pilon plate in treatment of type C Pilon fracture].

Objective: By comparing with traditional L-shaped plate, to explore the effectiveness of new Pilon plate in the treatment of type C Pilon fracture. Methods: A clinical data of 57 patients with type C Pilon fractures who met the selection criteria between May 2018 and January 2020 was analyzed retrospectively. Thirty-two patients were treated with new Pilon plate (trial group) and 25 patients with traditional L-shaped plate (control group). There was no significant difference in gender, age, cause of injury, fracture side and type, the interval between injury and operation between the two groups (P>0.05). The operation time and complications of the two groups were recorded. X-ray films were taken after operation to assess the quality of fracture reduction according to the Burwell-Charnley classification and fracture healing. Ankle function was evaluated according to Johner-Wruhs scoring standard and American Orthopaedic Foot and Ankle Society (AOFAS) score. Results: The operations of the two groups were completed successfully, and the operation time of the trial group was significantly shorter than that of the control group (t=-3.025, P=0.005). After operation, the incision necrosis occurred in 2 cases of the control group, and the incisions of other patients in both groups healed by first intention. All patients were followed up 8-16 months, with an average of 10.1 months. There was no significant difference in follow-up time between the two groups (t=0.433, P=0.667). X-ray films showed that the ankle reduction of the trial group was rated as excellent in 28 cases and good in 4 cases, with an excellent and good rate of 100%, while in the control group, the ankle reduction was rated as excellent in 15 cases, good in 5 cases, and fair in 5 cases, with an excellent and good rate of 80.0%. There was a significant difference in the excellent and good rate of fracture reduction between the two groups (Z=-2.565，P=0.010). The fracture healed in both groups, and the healing time was (16.59±3.78) weeks in the trial group and (17.80±3.81) weeks in the control group, and there was no significant difference between the two groups (t=-1.191, P=0.239). At last follow-up, according to Johner-Wruhs scoring standard, the ankle joint function in the trial group was evaluated as excellent in 25 cases and good in 7 cases, with an excellent and good rate of 100%; the AOFAS score was 90.9±4.5. In the control group, 16 cases were excellent, 5 cases were good, and 4 cases were fair, and the excellent and good rate was 84.0%; the AOFAS score was 85.2±10.0. The ankle function scores of the trial group was superior to that of the control group (P<0.05). During follow-up, except for 1 case of ankle traumatic arthritis in the control group, there was no complication such as ankle malunion, plate loosening and fracture, or fracture reduction loss in both groups. Conclusion: Compared with the traditional L-shaped plate, the new Pilon plate in the treatment of type C Pilon fracture has the advantages of high reduction quality, reliable fixation, less irritation to soft tissue, high fracture healing rate, and satisfactory functional recovery of ankle joint.

Comprehensive evaluation of biopolymer immune implants for peritoneal metastasis carcinoma therapy.

Immunotherapy has been widely used in the treatment of advanced stage cancers with spreading metastases, while the fully activation of immune system often requires sustained and long-acting immune stimulation by immunotherapeutic agents. In previous studies, we designed a biopolymer immune implant by dynamic covalent bonds and achieved sustained release of loaded immunotherapeutic agents, thus stimulated systemic immune activation and elicited immune memory effects. Herein, we further optimized the implants and carried out a comprehensive evaluation of the implants on peritoneal metastasis carcinoma (PMC) therapy. Our results showed that the implants fabricated with 8-arm polyethylene glycol amine (8-arm PEG-NH2) and 40% oxidation degree dextran (ODEX) exhibited a satisfactory degradation time for activating the antitumor immunity. The drug combination of oxaliplatin (OxP) and resiquimod (R848) could be sustainably released from the implants for 18 days. The implants cured 75% of mice with PMC and elicited immune memory effects to resist tumor re-challenge without obvious side effects observed. Mechanism analysis revealed that the implants could serve as an in-situ vaccine to enhance the infiltration of activated dendritic cells (DCs), T cells and natural killer (NK) cells inside the tumor, as well as increase the serum tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin 12 (IL-12) levels. These results strongly support the clinical translation potential of this sustained released biopolymer immune implants for PMC therapy.

Within-patient randomised clinical trial exploring the development of microskin implantation in the treatment of pressure ulcers.

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.

The intrarenal landscape of T cell receptor repertoire in clear cell renal cell cancer.

BACKGROUND: Clear cell renal cell cancer (ccRCC) is accompanied by T-cell infiltration. In this study, we sought to determine the difference in T-cell infiltration and the T-cell receptor (TCR) immune repertoire between ccRCC and peritumour tissue. METHODS: T-cell infiltration was examined using immunohistochemistry (IHC) and haematoxylin and eosin (HE) staining. The chi-squared test and Pearson correlation analysis were applied to evaluate the relationship between clinical traits and CD3, CD4, and CD8 expression. Immune repertoire sequencing (IR-Seq) was used to describe the profile of the TCR repertoire. RESULTS: The adjacent tissue showed increased expression of CD3, CD4 and CD8 compared with ccRCC tissue (PCD3 = 0.033; PCD4 = 0.014; PCD8 = 0.004). Indicated CD3+ T-cell density in ccRCC tissue was positively correlated with that in peritumour tissue (P = 0.010, r = 0.514), which implied the T cells in peritumour tissue directly infect the number of cells infiltrating in ccRCC tissue. Moreover, there was a positive correlation between Vimentin expression and indicated positive T-cell marker in ccRCC tissue (PCD3 = 0.035; PCD4 = 0.020; PCD8 = 0.027). Advanced stage revealed less CD4+ T-cell infiltration in ccRCC tissue (PCD4 = 0.023). The results from IR-Seq revealed an obvious increase in VJ and VDJ segment usage, as well as higher complementarity-determining region 3 (CDR3) amino acid (aa) clonotypes in ccRCC. The matched antigen recognized by the TCR of ccRCC may be potential targets. CONCLUSIONS: The current study collectively demonstrates diminished T-cell infiltration and increased CDR3 aa diversity in ccRCC, which may be associated with immunotherapeutic targets for ccRCC patients.