White-Light Emission from a Host-Guest Composite between Carboxylatopillar[5]arene-Modified N-Doped Carbon Dots and Rhodamine 6G for Rutin Detection.

The construction of tunable white-light-emitting materials has garnered increasing attention in the scientific community. In this study, N-doped carbon dots (N-CDs) were surface-modified with carboxylatopillar[5]arene (CP[5]) using an EDC-NHS coupling reaction to create CCDs. CCDs were then conjugated with rhodamine 6G (R6G) through host-guest interactions to fabricate the CCDs-R6G composites. These composites produced two-color fluorescence emission peaks at 447 and 557 nm when excited by a wavelength of 340 nm. Excitingly, white-light emission (0.28, 0.30) can be readily achieved by varying the R6G concentration. To further explore potential applications, a new detection method for rutin (RT) based on the inner filter effect (IFE) was developed. Experimental results verify the practicality and reliability of the fluorescence sensor based on CCDs-R6G composites for RT detection in real samples.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Comparison of Ba-Hao burn ointment gauze and petrolatum gauze in split graft donor site healing: A randomized, prospective, and self-control study.

Background and Aims: To assess patient comfort, wound healing, and scarring at the 6-month follow-up of split-skin graft donor sites treated with Ba-Hao burn ointment (BHBO) gauze, a compound preparation of traditional Chinese medicine since 1970s, compared with petrolatum gauze. Methods: Thirty patients admitted to the Department of Burns of the First Affiliated Hospital of Anhui Medical University between September 2021 and September 2022 participated in this randomized, prospective, self-control clinical study. After harvesting the split skin, donor sites were divided into two parts along the midline. BHBO gauze was applied to half of the donor wounds, and petrolatum gauze was applied to the other half. The wound healing time, pain scores on the postoperative Days 3, 6, and 9, and Vancouver Scar Scale (VSS) score at the 6-month follow-up were assessed. Results: The wound healing time was significantly shorter in the BHBO group than in the control group (10.07 ± 1.48 days vs. 11.50 ± 1.74 days, p < 0.001). On postoperative Days 3 and 6, the pain scores quantified by visual analog scores were significantly lower in the BHBO group than in the control group (5.33 ± 1.54 and 4.17 ± 1.51, respectively vs. 7.57 ± 1.41 and 5.20 ± 1.47, respectively). The difference in the visual analog scale score on postoperative Day 9 between the groups was not significant (p > 0.05). Microbiological assessment revealed the absence of bacterial contamination in both groups. At the 6-month follow up, the VSS score was significantly lower in the BHBO group (6.67 ± 1.92) than in the control group (9.57 ± 1.55). Conclusion: BHBO resulted in faster donor-site healing, reduced postoperative pain, and improved scar quality at the 6-month follow-up than petrolatum gauze alone.

First-In-Human Study on Pharmacokinetics, Safety, and Tolerability of Single and Multiple Escalating Doses of PA9159 Nasal Spray, a Highly Potent Glucocorticoid in Healthy Chinese Volunteers.

OBJECTIVE: PA9159 (previously named VSG159) is a structurally novel and highly potent glucocorticoid that plays a role in the late development of autoimmune and inflammatory diseases. The current first-in-human ascending-dose study of the PA9159 nasal spray was conducted in healthy Chinese volunteers to evaluate its pharmacokinetics, safety, and tolerability. In addition, the effects of PA9159 on serum cortisol secretion were investigated. METHODS: This was a double-blinded, randomized, placebo-controlled clinical study that included four single-dose groups in the single ascending dose cohort (SAD) and two multiple-dose groups in the multiple ascending dose cohort (MAD), with dose ranges of 10-80 µg and 20-40 µg, respectively. PA9159 was administered bilaterally via nasal spray once only or once daily for seven days. Pharmacokinetic, safety, and tolerability profiles were evaluated. RESULTS: A total of 60 participants completed the study. PA9159 doses of up to 80 µg in the SAD and up to 40 µg in the MAD were shown to be safe and tolerable. The most common treatment-related AEs were mild and transient local nasal AEs. Morning serum cortisol levels approximately remained unchanged in both the single-dose and multiple-dose groups. PA9159 was quantified in 41.8% (368/880) of the samples in all treatment groups, including 25.2% (105/416) of the SAD and 56.7% (263/464) of the MAD. The majority (>80.0%) of PA9159 plasma concentrations ranged from 0.5 to 2 pg/mL in determined samples. The mean AUC0-t of PA9159 in the SAD was 0.91, 1.39±0.68, 11.40±9.91, and 46.30±25.80 h*pg/mL in the 10 to 80 ug single group. The mean terminal half-life time (t1/2) was 8.43 h and 8.97±2.28 h in 40 ug and 80 ug single group, respectively. The mean AUCss of PA9159 in the MAD was 31.70±7.04, 44.20±20.60 h*pg /mL, and the t1/2 was 16.00±4.18 h, 21.20±10.20 h in the 20 ug and 40 ug multiple groups, respectively. The median Tmax was approximately 6 hours in both the SAD and MAD cohorts. CONCLUSIONS: The PA9159 nasal spray was generally safe and well tolerated, and the effects of PA9159 on serum cortisol levels were limited. The plasma concentration and systemic exposure to PA9159 were very low. These findings support the necessity for further clinical studies on PA9159 nasal spray in patients suffering from allergic rhinitis.

MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

Bibliometric analysis of worldwide research on Polycythemia Vera in the 21st century.

Polycythemia vera (PV) is a myeloproliferative tumor with low incidence and complex symptoms, affecting patients' quality of life and shortening their life span. Since the beginning of the 21st century, there has been an update but a need for uniform consensus regarding diagnosing and treating PV. With the continued interest of researchers in this field, a bibliometric study of PV is necessary. This paper aims to analyze articles on PV through bibliometric software to provide collaborative information and new ideas for researchers in this field. We collected PV-related publications in the Web of Science Core Collection database from 2000 to 2023. The included literature was analyzed using Citespace (6.2.R2), VOSviewer (1.6.19), and Bibliometrix. The study included country/region, institution, authors, journals, keywords, and references, and a visual knowledge network diagram was constructed. Microsoft Excel 2013 was also used for statistical analysis. A total of 1,093 articles were eventually included. The number of PV-related publications has steadily increased from 2000 to the present, with great potential for future growth. The US and US institutions have contributed more to this field, with the US ranking first in the number of publications, total citations, and centrality. Alessandro M. Vannucchi is the most published author. Tefferi, Ayalew is the most cited author. And BLOOD has the most publications, topping the list of the eleven high-productivity core source journals. The most cited article was "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders" (Baxter, EJ, 2005). By examining the keywords, we found that the diagnosis and typing of true erythrocytosis, the use of ruxolitinib, and the tyrosine kinase JAK2 are the research hotspots in the field; genetic and molecular research in the field of true erythrocytosis is a cutting-edge topic in the field; and risk factors for true erythrocytosis is a cutting-edge hotspot issue in the field. The fruitful research in this century has laid the foundation for developing the field of PV. The information in this article will provide researchers with current hotspots and future potential in the discipline, helping the field achieve more extraordinary breakthroughs. Currently, research should focus on increasing global multicenter collaborative research in diagnosis and treatment to develop scientifically recognized diagnostic and treatment protocols and new clinical drug research. Our proposed model of global innovation collaboration will provide strong support for future research.

Serum phosphate levels and the development of sepsis associated acute kidney injury: evidence from two independent databases.

Objective: We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI). Methods: Septic patients from the Medical Information Mart for Intensive Care IV (MIMIC IV) and the eICU Collaborative Research Database (eICU-CRD) were enrolled. Restricted cubic spline (RCS) was used to visualize the relationship between phosphate levels and the risk of SAKI. Patients were divided into four categories based on their serum phosphate levels. Logistic regression analysis, receiver operating characteristic (ROC) curve and subgroup analysis were performed to evaluate the predictive value of serum phosphate for SAKI. Results: A total of 9,244 and 2,124 patients from the MIMIC IV and eICU-CRD database were included in the final analysis. RCS curve revealed a non-linear correlation between phosphate levels and the risk of SAKI (p for non-linearity <0.05). Each 1 mg/dL increase in phosphate levels was associated with a 1.51 to 1.64-fold increased risk of SAKI (OR 2.51-2.64, p < 0.001) in the MIMIC IV cohort and a 0.29 to 0.38-fold increased risk (OR 1.29-1.38, p < 0.001) in the eICU-CRD cohort. Compared to the normal-low category, hyperphosphatemia and normal-high category were independently associated with an increased risk of SAKI, while hypophosphatemia was independently associated with a decreased risk in the MIMIC IV cohort. A similar trend was observed in the eICU-CRD cohort, but statistical significance disappeared in the hypophosphatemia category and the adjusted model of normal high category. These finding was consistent in subgroup analysis. Conclusion: Elevated serum phosphate, even within the normal range, is an independent risk factor for developing SAKI in septic patients. Abnormal change in serum phosphate levels may be a novel biomarker for early prediction of SAKI occurrence.

Ultrafast piezocapacitive soft pressure sensors with over 10 kHz bandwidth via bonded microstructured interfaces.

Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.

Naked-Eye 3-Dimensional Vision Training for Myopia Control: A Randomized Clinical Trial.

Importance: Early onset of myopia increases the risk of high myopia, which can lead to irreversible retinal damage and even loss of central vision. Objective: To investigate the efficacy and safety of naked-eye 3-dimensional vision training (NVT) in preventing the progression of myopia in children. Design, Setting, and Participants: This randomized clinical trial was conducted in 3 hospitals from May 25, 2022, to February 24, 2023. Participants were children (aged 6-18 years) who had a diagnosis of myopia with a spherical equivalent refraction of -0.75 to -6.00 diopters (D). Intervention: Children in the intervention group received 20 minutes of NVT treatment every day, whereas children in the control group lived as usual without vision training. Main Outcome and Measure: The primary outcome was the change in axial length at 6 months. Spherical equivalent refraction (SER) was included as a secondary outcome. Results: Among 263 participants, 125 (47.5%) were male and 138 (52.5%) were female; the mean (SD) age was 10.3 (1.9) years (range, 6.1-15.6 years). A total of 227 patients (86.3%) completed the 6-month follow-up, including 102 in the intervention group and 125 in the control group. In the intervention group, the changes in axial length and SER at 6 months were 0.18 mm (95% CI, 0.16 to 0.20 mm) and -0.25 D (95% CI, -0.31 to -0.19 D), respectively. In the control group, the changes in axial length and SER at 6 months were 0.23 mm (95% CI, 0.21 to 0.25 mm) and -0.35 D (95% CI, -0.41 to -0.30 D), respectively. The differences in AL and SER between the 2 groups were significant (AL difference: -0.06 mm; 95% CI, -0.09 to -0.03; P < .001; SER difference: 0.10 D; 95% CI, 0.02 to 0.19; P = .02). No study-related adverse reactions were reported during follow-up. Conclusions and Relevance: NVT is a safe and promising means to control myopia progression in children with good adherence. Trial Registration: ClinicalTrials.gov Identifier: NCT05468775.

An abdominal vibration combined with walking exercise (AVCWE) program for older patients with constipation: Development and feasibility study.

BACKGROUND: Older patients with constipation are at higher risk for inadequate bowel preparation, but there are currently no targeted strategies. This study aims to develop an abdominal vibration combined with walking exercise (AVCWE) program and assess its feasibility among older patients with constipation. METHODS: Phase I: Using the Delphi technique, eight experts across three professional fields were consulted to develop the AVCWE program. The experts evaluated and provided recommendations on demonstration videos and detailed descriptions of the preliminary protocol. Phase II: A single-arm feasibility study of the AVCWE program was conducted on 30 older patients with constipation undergoing colonoscopy at a tertiary hospital in China. A 10-point exercise program evaluation form and several open-ended questions were used to gather feedback from participants regarding the program. In both phases, content analysis was used to critically analyze and summarize qualitative suggestions for protocol modifications. RESULTS: Based on feedback from the expert panel, the AVCWE program developed in Phase I included two procedures during laxative ingestion: at least 5,500 steps of walking exercise and two cycles of moderate-intensity abdominal vibration (each cycle consisted of 10 min of vibration and 10 min of rest). The feasibility study in Phase II showed high positive patient feedback scores for the program, ranging from 9.07 ± 0.74 to 9.73 ± 0.52. CONCLUSION: The AVCWE program was developed by eight multidisciplinary experts and was well accepted by 30 older patients with constipation. Study participants believed that this program was simple, safe, appropriate, and helpful for their bowel preparation. The findings of this study may provide valuable information for optimizing bowel preparation in older patients with constipation.

[Energy-saving and Emission Reduction Path for Road Traffic in Key Coastal Cities of Guangdong, Fujian and Zhejiang].

The rapid development of society and economy has resulted in a substantial increase in energy consumption, consequently exacerbating pollution issues. Current research predominantly focuses on energy-saving and emission reduction in road transportation within individual cities or the three major economic regions of China:the Yangtze River Delta, the Pearl River Delta, and the Beijing-Tianjin-Hebei Region. However, there is a dearth of studies addressing the southeastern coastal economic region. Located at the heart of China's southeastern coastal economic development, the provinces of Guangdong, Fujian, and Zhejiang unavoidably face challenges associated with energy consumption and emissions while pursuing economic growth. To address these challenges, this study employed a LEAP model to construct various scenarios for road transportation in the key coastal cities of Guangdong, Fujian, and Zhejiang from 2015 to 2035. These scenarios included a baseline scenario (BAU), an existing policy scenario (EPS), and an improved policy scenario (MPS). The MPS and EPS encompassed vehicle structure optimization (VSO), improved fuel economy (IFE), and reduced annual average mileage (RDM). By simulating and evaluating these scenarios, the energy-saving and emission reduction potentials of road transportation in the key coastal cities were assessed. The results indicated that, in the primary scenario, the MPS exhibited the most significant improvements in energy-saving, carbon reduction, and pollutant reduction effects. By 2035, the MPS achieved a remarkable 75% energy-saving rate compared to that in the baseline scenario, accompanied by reductions of 68%, 59%, 66%, 70%, and 64% in CO2, CO, NOx, PM2.5, and SO2 emissions, respectively. In the secondary scenario, the improved scenario of enhancing fuel economy achieved a notable 30% reduction in energy consumption. Additionally, the scenarios involving vehicle structure adjustment (yielding reductions of 36%, 30%, 36%, 26%, and 40%) and annual average mileage reduction (resulting in reductions of 37%, 37%, 36%, 37%, and 36%) demonstrated significant reductions in CO2, CO, NOx, PM2.5, and SO2 emissions.

Nomograms for predicting prognostic value of combined neutrophil-to-lymphocyte ratio and SCC-Ag in locally advanced cervical cancer.

Background: Accumulating evidence supports the important role of inflammation in tumorigenesis and progression. Squamous cell carcinoma-associated antigen (SCC-Ag) is a tumor marker widely used to predict the prognosis of patients with cervical squamous cell carcinoma. This paper explored the predictive value of combined detection of neutrophil-to-lymphocyte ratio (NLR) to SCC-Ag for prognosis in patients with locally advanced cervical cancer (LACC). Methods: A retrospective analysis was conducted on 190 LACC patients who underwent concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016. NLR and SCC-Ag were analyzed before treatment. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cutoff point for NLR and SCC-Ag. Kaplan-Meier analysis and Cox regression analysis were performed to assess their prognostic values. Nomograms were established to predict progression-free survival (PFS) and overall survival (OS), and the Harrell's concordance index (C-index) was introduced to evaluate the accuracy of predictions. Results: The optimal cutoff values for SCC-Ag and NLR were 3.25 ng/mL and 2.52, respectively. Patients with SCC-Ag >3.25 ng/mL and NLR >2.52 were significantly associated with decreased PFS and OS. Multivariate analysis indicated that SCC-Ag and NLR were independent prognostic factors for PFS (P=0.022 and P=0.004, respectively) and OS (P=0.031 and P=0.001, respectively). The area under the curve of SCC-Ag, NLR and their combination to predict PFS and OS of LACC were 0.688, 0.623, 0.708 and 0.684, 0.658, 0.723, respectively. C-index of nomograms based on PFS and OS were 0.725 [95% confidence interval (CI): 0.653-0.797] and 0.731 (95% CI: 0.658-0.804), respectively. Conclusions: The combination of SCC-Ag and NLR could provide a better predictive prognosis than SCC-Ag or NLR alone, and nomograms based on PFS and OS can be recommended as practical models for evaluating the prognosis of LACC patients.

JNK signaling mediates acute rejection via activating autophagy of CD8+ T cells after liver transplantation in rats.

Background: Acute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8+ T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8+ T cells. However, the underlying mechanisms regulating autophagy in CD8+ T cells during AR remain unclear. Methods: Human liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8+ T cells autophagy. The effect of JNK inhibition on CD8+ T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8+ T cells were further explored. Results: The expression of JNK is positive correlated with the autophagy level of CD8+ T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8+ T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8+ T cells. Mechanistically, JNK may activate the autophagy of CD8+ T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex. Conclusion: JNK signaling promoted CD8+ T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT.

The enhancement of energy supply in syngas-fermenting microorganisms.

After the second industrial revolution, social productivity developed rapidly, and the use of fossil fuels such as coal, oil, and natural gas increased greatly in industrial production. The burning of these fossil fuels releases large amounts of greenhouse gases such as CO2, which has caused greenhouse effects and global warming. This has endangered the planet's ecological balance and brought many species, including animals and plants, to the brink of extinction. Thus, it is crucial to address this problem urgently. One potential solution is the use of syngas fermentation with microbial cell factories. This process can produce chemicals beneficial to humans, such as ethanol as a fuel while consuming large quantities of harmful gases, CO and CO2. However, syngas-fermenting microorganisms often face a metabolic energy deficit, resulting in slow cell growth, metabolic disorders, and low product yields. This problem limits the large-scale industrial application of engineered microorganisms. Therefore, it is imperative to address the energy barriers of these microorganisms. This paper provides an overview of the current research progress in addressing energy barriers in bacteria, including the efficient capture of external energy and the regulation of internal energy metabolic flow. Capturing external energy involves summarizing studies on overexpressing natural photosystems and constructing semiartificial photosynthesis systems using photocatalysts. The regulation of internal energy metabolic flows involves two parts: regulating enzymes and metabolic pathways. Finally, the article discusses current challenges and future perspectives, with a focus on achieving both sustainability and profitability in an economical and energy-efficient manner. These advancements can provide a necessary force for the large-scale industrial application of syngas fermentation microbial cell factories.

Multistress Interplay: Time and Duration of Ocean Acidification Modulate the Toxicity of Mercury and Other Metals.

The current understanding of multistress interplay assumes stresses occur in perfect synchrony, but this assumption is rarely met in the natural marine ecosystem. To understand the interplay between nonperfectly overlapped stresses in the ocean, we manipulated a multigenerational experiment (F0-F3) to explore how different temporal scenarios of ocean acidification will affect mercury toxicity in a marine copepod Pseudodiaptomus annandalei. We found that the scenario of past acidification aggravated mercury toxicity but current and persistent acidification mitigated its toxicity. We specifically performed a proteomics analysis for the copepods of F3. The results indicated that current and persistent acidification initiated the energy compensation for development and mercury efflux, whereas past acidification lacked the barrier of H+ and had dysfunction in the detoxification and efflux system, providing a mechanistic understanding of mercury toxicity under different acidification scenarios. Furthermore, we conducted a meta-analysis on marine animals, demonstrating that different acidification scenarios could alter the toxicity of several other metals, despite evidence from nonsynchronous scenarios remaining limited. Our study thus demonstrates that time and duration of ocean acidification modulate mercury toxicity in marine copepods and suggests that future studies should move beyond the oversimplified scenario of perfect synchrony in understanding multistress interaction.

MATN2 overexpression suppresses tumor growth in ovarian cancer via PTEN/PI3K/AKT pathway.

The incidence rate of developing ovarian cancer decreases over the years; however, mortality ranks top among malignancies of women, mainly metastasis through local invasion. Matrilin-2 (MATN2) is a member of the matrilin family that plays an important role in many cancers. However, its relationship with ovarian cancer remains unknown. Our study aimed to explore the function and possible mechanism of MATN2 in ovarian cancer. Human ovarian cancer tissue microarrays were used to detect the MATN2 expression in different types of ovarian cancer using immunohistochemistry (IHC). CCK-8, wound scratch healing assay, transwell assay, and flow cytometry were used to detect cell mobility. Gene and protein expression were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. MATN2 interacts with phosphatase, and the tensin homolog (PTEN) deleted on chromosome 10 was analyzed using TCGA database and co-immunoprecipitation (Co-IP). In vivo experiments were conducted using BALB/c nude mice, and tumor volume and weight were recorded. Tumor growth was determined using hematoxylin and eosin (H&E) and IHC staining. MATN2 was significantly downregulated in ovarian cancer cells. The SKOV3 and A2780 cell mobility was significantly inhibited by MATN2 overexpression, while the cell apoptosis rate was significantly increased. MATN2 overexpression decreased transplanted tumor size in vivo. These results were reversed by inhibiting MATN2. Furthermore, we found that PTEN closely interacted with MATN2 using bioinformatics and Co-IP. MATN2 overexpression significantly inhibited the PI3K/AKT pathway, however, PTEN suppression reversed this effect of MATN2 overexpression. These results indicated that MATN2 may play a critical role in ovarian cancer development by inhibiting cells proliferation and migration. The mechanism was related to interacting with PTEN, thus inhibiting downstream effectors in the PI3K/AKT pathway, which may be a novel target for treating ovarian cancer.

Unusual optical phenomena inside and near a rotating sphere: the photonic hook and resonance.

Based on the optical Magnus effect, the analytical expressions of the electromagnetic field that a spinning dielectric sphere illuminated by polarized plane waves are derived according to the "instantaneous rest-frame" hypothesis and Minkowski's theory. More attention is paid to the near field. The unusual optical phenomena in mesoscale spheres without material and illumination wave asymmetry that are the photonic hook (PH) and whispering gallery mode (WGM)-like resonance caused by rotation are explored. The impact of resonance scattering on PHs is further analyzed under this framework. The influence of non-reciprocal rotating dimensionless parameter γ on PH and resonance is emphasized. The results in this paper have extensive application prospects in mesotronics, particle manipulation, resonator design, mechatronics, and planetary exploration.