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Renal ischemia-reperfusion injury (RIRI) is a common pathological process that causes kidney injury. Previous studies have indicated that both peroxisome proliferator-activated receptor γ (PPARγ) and microRNA-21 (miR-21) exert protective effects against RIRI. However, their relationship is not well understood. In the present study, we investigated the role of the PPARγ/miR-21/programmed cell death 4 (PDCD4) axis in IRI, both in vivo and in vitro. In vitro cell hypoxia/reoxygenation (H/R) and in vivo RIRI models were established, and cell viability, cell apoptosis, and key molecule expression profiles were analyzed. Our results showed that both PPARγ and miR-21 had protective effects against RIRI to varying degrees, and there was an interaction between PPARγ and miR-21. PPARγ could promote the expression of miR-21 and partially protect against RIRI by reducing the level of the miR-21 target protein (PDCD4). Our findings underscore the potential utility of future clinical investigations of PPARγ activation and targeting of the underlying miR-21/PDCD4/caspase-3 pathway, which may participate in the pathogenesis of human IRI.

Multicolor organic room temperature phosphorescence (RTP) has garnered wide research attention due to the long luminescence lifetime and tunable excited state properties, which show great potential in displays, anticounterfeiting, data encryption, and sensing. However, because of the sensitivity of triplet excitons of organic materials, the triplet emitting level of organic compounds is hard to manipulate. Therefore, realizing multicolor RTP in organic materials is still a huge challenge. In this review, we summarize recent advances in multicolor organic RTP materials, including the underlying luminescence mechanisms, design principles of multicolor phosphorescence, detailed photophysical behaviors, and their potential applications. The last part presents existing challenges and future perspectives, such as expanding the color gamut, enriching stimuli-responsive properties, improving the phosphorescence performance, and exploring more advanced applications. This review will provide inspiration and guidelines for constructing multicolor RTP materials and expanding their potential applications in organic electronics, bioelectronics, flexible electronics, and so on.

Background Aparapotamon, a freshwater crab genus endemic to China, includes 13 species. The distribution of Aparapotamon spans the first and second tiers of China's terrain ladder, showing great altitudinal differences. To study the molecular mechanisms of adaptive evolution in Aparapotamon, we performed evolutionary analyses, including morphological, geographical, and phylogenetic analyses and divergence time estimation. We sequenced the mitogenomes of Aparapotamon binchuanense and Aparapotamon huizeense for the first time and resequenced three other mitogenomes of Aparapotamon grahami and Aparapotamon gracilipedum. These sequences were combined with NCBI sequences to perform comparative mitogenome analysis of all 13 Aparapotamon species, revealing mitogenome arrangement and the characteristics of protein-coding and tRNA genes. Results A new species classification scheme of the genus Aparapotamon has been detected and verified by different aspects, including geographical, morphological, phylogenetics and comparative mitogenome analyses. Imprints from adaptive evolution were discovered in the mitochondrial genomes of group A, including the same codon loss at position 416 of the ND6 gene and the unique arrangement pattern of the tRNA-Ile gene. Multiple tRNA genes conserved or involved in adaptive evolution were detected. Two genes associated with altitudinal adaptation, ATP8 and ND6, which experienced positive selection, were identified for the first time in freshwater crabs. Conclusions Geological movements of the Qinghai-Tibet Plateau and Hengduan Mountains likely strongly impacted the speciation and differentiation of the four Aparapotamon groups. After some group A species dispersed from the Hengduan Mountain Range, new evolutionary characteristics emerged in their mitochondrial genomes, facilitating adaptation to the low-altitude environment of China's second terrain tier. Ultimately, group A species spread to high latitudes along the upper reaches of the Yangtze River, showing faster evolutionary rates, higher species diversity and the widest distribution.

Metabolic reprogramming refers to the transformation of the whole metabolic network covering glycolysis and mitochondrial metabolism, which is primarily manifested as the Warburg effect and mitochondrial metabolic reprogramming. Propofol (Pro) has been testified to suppress the malignancy of diversified human cancers. Nevertheless, its role in glycolysis is still uncertain. The purpose of this study was to determine whether Pro modulated glycolysis in ovarian cancer (OC) cells. Cell proliferation, apoptosis, migration, and invasion were tested via CCK-8, flow cytometry, and Transwell assays, respectively, and glucose intake, lactic acid, and ATP production were also determined. Pro restrained glycolysis via mediating the circular RNA-zinc finger RNA-binding protein (ZFR)/microRNA (miR)-212-5p/superoxide dismutase 2 (SOD2) axis. Additionally, Pro restrained cancer cell advancement via modulating circ-ZFR/miR-212-5p/SOD2 axis. In short, Pro restrained glycolysis via mediating the circ-ZFR/miR-212-5p/SOD2 axis. These results offered a better theoretical foundation for comprehending the molecular pathology of OC and provided a novel target for OC diagnosis and treatment.

Supplementary Table S1. GFP-NAT10s, construction and subcellular localization; Supplementary Table S2. Primers used in PCR-direct sequencing for the 28 exons of NAT10gene (Gene ID: 55226); Supplementary Table 3: Correlations between cytoplasmic/membranous staining of NAT10 and nuclear translocation of β-catenin in CRCs; Supplementary Table S4. Correlations between cytoplasmic/membranous staining of NAT10 and staining of E-cadherin and GSK-3β; TableS5. Correlations between NAT10 membranous staining and clinicopathologic parameters in CRCs.

Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive “leading edge” of the tumor. This correlated well with nuclear accumulation of β-catenin (P < 0.001; χ2 = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values < 0.001), and was associated with a poorer prognosis (P = 0.023; χ2 = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility.Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. Clin Cancer Res; 20(17); 4717–29. ©2014 AACR.

IntroductionThe underlying pathophysiological mechanisms of cerebral ischemia reperfusion injury (CIRI) is intricate, and current studies suggest that neuron, astrocyte, microglia, endothelial cell, and pericyte all have different phenotypic changes of specific cell types after ischemic stroke. And microglia account for the largest proportion after CIRI. Previous transcriptomic studies of ischemic stroke have typically focused on the 24 hours after CIRI, obscuring the dynamics of cellular subclusters throughout the disease process. Therefore, traditional methods for identifying cell types and their subclusters may not be sufficient to fully unveil the complexity of single-cell transcriptional profile dynamics caused by an ischemic stroke.MethodsIn this study, to explore the dynamic transcriptional profile of single cells after CIRI, we used single-cell State Transition Across-samples of RNA-seq data (scSTAR), a new bioinformatics method, to analyze the single-cell transcriptional profile of day 1, 3, and 7 of transient middle cerebral artery occlusion (tMCAO) mice. Combining our bulk RNA sequences and proteomics data, we found the importance of the integrin beta 2 (Itgb2) gene in post-modeling. And microglia of Itgb2+ and Itgb2- were clustered by the scSTAR method. Finally, the functions of the subpopulations were defined by Matescape, and three different time points after tMCAO were found to exhibit specific functions.ResultsOur analysis revealed a dynamic transcriptional profile of single cells in microglia after tMCAO and explored the important role of Itgb2 contributed to microglia by combined transcriptomics and proteomics analysis after modeling. Our further analysis revealed that the Itgb2+ microglia subcluster was mainly involved in energy metabolism, cell cycle, angiogenesis, neuronal myelin formation, and repair at 1, 3, and 7 days after tMCAO, respectively.DiscussionOur results suggested that Itgb2+ microglia act as a time-specific multifunctional immunomodulatory subcluster during CIRI, and the underlying mechanisms remain to be further investigated.

Cell-state transition can reveal additional information from single-cell ribonucleic acid (RNA)-sequencing data in time-resolved biological phenomena. However, most of the current methods are based on the time derivative of the gene expression state, which restricts them to the short-term evolution of cell states. Here, we present single-cell State Transition Across-samples of RNA-seq data (scSTAR), which overcomes this limitation by constructing a paired-cell projection between biological conditions with an arbitrary time span by maximizing the covariance between two feature spaces using partial least square and minimum squared error methods. In mouse ageing data, the response to stress in CD4+ memory T cell subtypes was found to be associated with ageing. A novel Treg subtype characterized by mTORC activation was identified to be associated with antitumour immune suppression, which was confirmed by immunofluorescence microscopy and survival analysis in 11 cancers from The Cancer Genome Atlas Program. On melanoma data, scSTAR improved immunotherapy-response prediction accuracy from 0.8 to 0.96.

Macrophage polarization plays an important role in asthma. Nuclear receptor corepressor 1 (NCOR1) plays an important role in metabolic and cardiovascular diseases by regulating the function of macrophages. The aim of this research was to examine the role and mechanism of macrophage NCOR1 in the development of asthma. We used ovalbumin (OVA) to induce macrophage NCOR1-deficient mice for asthma formation. Our results revealed that macrophage NCOR1 deficiency markedly enhanced allergic airway inflammation. In addition, NCOR1 deficiency in macrophages was found to enhance M2 polarization. Mechanistic studies suggested that NCOR1 promoted macrophage polarization by interacting with PPARγ, contributing to the pathogenesis of asthma. In conclusion, macrophage NCOR1 deficiency promoted the regulation of M2 programming by derepressing PPARγ expression to exacerbate asthma. Macrophage NCOR1 might be a potential target for the treatment of asthma.

Background The risk factors for osteoporosis and its prognostic value in patients with bronchiectasis is not well characterized. We explored the risk factors for osteoporosis and its prognostic impact in hospitalized non-cystic fibrosis bronchiectasis (NCFB) patients in Southeast China. Methods This observational cohort study consecutively enrolled 179 hospitalized patients with NCFB bronchiectasis between 2017 and 2021. The risk factors and the impact of osteoporosis on all-cause mortality were assessed. Results 21.2% (38/179) of hospitalized NCFB patients were diagnosed with osteoporosis. Patients with osteoporosis had more severe symptoms (assessed by chronic airway assessment test, CAT, median 22 vs. 17, P = 0.017), poorer quality of life (assessed by St. George Respiratory Questionnaires, SQRC, median 42 vs. 27, P = 0.007), more severe disease stage (assessed by bronchiectasis severity index, BSI, median 14 vs. 11, P = 0.02), more comorbidities (assessed by Bronchiectasis Aetiology Comorbidity Index, BACI, median 5 vs. 4, P = 0.021) than patients without. Age, female sex, anemia, post-infection, and history of regular inhaled corticosteroid treatment were independent risk factors for osteoporosis in those patients. 21 patients (11.7%) died over a median follow-up period of 32 months. The all-cause mortality in NCFB patients with osteoporosis [28.94% (11/38)] was significantly higher than those without osteoporosis [7.09% (10/141)] [hazard ratio (HR) 5.34, 95% confidence interval (CI) 2.26–12.67, P P Conclusions Osteoporosis had an independent effect on all-cause mortality in hospitalized NCFB patients. Management of comorbidities, including bone health, is a critical aspect of treating NCFB patients.

The molecular mechanisms underlying the recognition of epitopes by T cell receptors (TCRs) are critical for activating T cell immune responses and rationally designing TCR-based therapeutics. Single-cell sequencing techniques vastly boost the accumulation of TCR sequences, while the limitation of available TCR-pMHC structures hampers further investigations. In this study, we proposed a comprehensive strategy that incorporates structural information and single-cell sequencing data to investigate the epitope-recognition mechanisms of TCRs. By antigen specificity clustering, we mapped the epitope sequences between epitope-known and epitope-unknown TCRs from COVID-19 patients. One reported SARS-CoV-2 epitope, NQKLIANQF (S919-927), was identified for a TCR expressed by 614 T cells (TCR-614). Epitope screening also identified a potential cross-reactive epitope, KLKTLVATA (NSP31790-1798), for a TCR expressed by 204 T cells (TCR-204). According to the molecular dynamics (MD) simulations, we revealed the detailed epitope-recognition mechanisms for both TCRs. The structural motifs responsible for epitope recognition revealed by the MD simulations are consistent with the sequential features recognized by the sequence-based clustering method. This strategy will facilitate the discovery and optimization of TCR-based therapeutics. In addition, the comprehensive strategy can also promote the development of cancer vaccines in virtue of the ability to discover neoepitopes and epitope-recognition mechanisms.

With a high prevalence of morbidity and mortality, myocardial infarction (MI) is a prevalent heart disease. The development and outcomes of post-MI heart failure (HF) continue to be a major factor in the poor post-MI prognosis despite the extensive medical treatment for MI. There are currently few indicators that can accurately predict post-MI heart failure. In this study, we re-examined single cell RNA-seq and bulk RNA-seq datasets collected from peripheral blood samples of myocardial infarction and dataset of patients who developed heart failure or heart failure did not occur after myocardial infarction. We discovered a subtype of immune-activation B cell which is associated with the discrimination of post-MI HF and nonHF patients. Such finding was further validated in independent corhorts using PCR. By incorporating the specific marker genes of the B subtype, we developed a prediction model with 13 markers that can predict the HF risk of myocardial infarction patients and provide useful clinical experience and tools.

Renal cell carcinoma (RCC) seriously threatens people's lives and health. The identification of some precise biomarkers during the process of RCC progression and the pathophysiologic procedure is critical for improving the diagnosis and management of RCC. Evidence suggests that ferroptosis may play a pivotal role in eradicating clear cell RCC (ccRCC, KIRC) tumor cells. We screened out the target prognostic ferroptosis-associated genes and examined the functions of farnesyl-diphosphate farnesyltransferase (FDFT1) in 786-O cells by plasmid transfection. In our study, we identified FDFT1 as a potential marker correlating with ferroptosis in KIRC. Upregulated FDFT1 inhibited cell proliferation, migration, and invasion, and the underlying antitumor effects may occur via the AKT signaling pathway. Our study provides helpful evidence to study the complex physiopathology of KIRC.

Increasing evidence has been confirmed that small nucleolar RNAs (SnoRNAs) play critical roles in tumorigenesis and exhibit prognostic value in clinical practice. However, there is short of systematic research on SnoRNAs in ovarian cancer (OV).379 OV patients with RNA-Seq and clinical parameters from TCGA database and 5 paired clinical OV tissues were embedded in our study. Cox regression analysis was used to identify prognostic SnoRNAs and construct prediction model. SNORic database was adopted to examine the copy number variation of SnoRNAs. ROC curves and KM plot curves were applied to validate the prognostic model. Besides, the model was validated in 5 paired clinical tissues by real-time PCR, HE staining and immunohistochemistry.A prognostic model was constructed on the basis of SnoRNAs in OV patients. Patients with higher RiskScore had poor clinicopathological parameters, including higher age, larger tumor size, advanced stage and with tumor status. KM plot analysis confirmed that patients with higher RiskScore had poorer prognosis in subgroup of age, tumor size, and stage. 7 of 9 SnoRNAs in the prognostic model had positive correlation with their host genes. Moreover, 5 of 9 SnoRNAs in the prognostic model correlated with their CNVs, and SNORD105B had the strongest correction with its CNVs. ROC curve showed that the RiskScore had excellent specificity and accuracy. Further, results of HE staining and immunohistochemistry of Ki67, P53 and P16 confirmed that patients with higher RiskScore are more malignant.In summary, we identified a nine-SnoRNAs signature as an independent indicator to predict prognosis of OV, providing a prospective prognostic biomarker and potential therapeutic targets for ovarian cancer.

Gliomas, the most prevalent brain tumors, account for nearly one-third of the all brain and central nervous system (CNS) tumors diagnosed in the USA. The purpose of this study was to discuss the important role of A kinase-interacting protein 1 (AKIP1) in glioma and reveal the potential mechanism. After prediction by CCLE, the expression of AKIP1 was determined by qRT-PCR and western blot. The impacts of AKIP1 knockdown on the proliferation, migration, and invasion were then measured by MTT, colony formation assay, wound healing, and transwell assays. Western blot was used to assess the protein levels of migration and epithelial-mesenchymal transition- (EMT-) related factors. Subsequently, the expression of Disks Large Homolog 2 (DLG2) was predicted by bioinformatics analyses, and the interaction between AKIP1 and DLG2 was confirmed by IP assay, qRT-PCR, and western blot. Finally, DLG2 was further downregulated in glioma cells to detect the association between AKIP1 and DLG2 in the cellular functions of glioma. It was demonstrated that AKIP1 exhibited a high level in glioma cells, and interference of AKIP1 led to reductions in the proliferation, migration, invasion, and EMT of glioma cells. DLG2, which was lowly expressed in glioma cells, demonstrated a negative link to AKIP2. Inhibition of both AKIP2 and DLG2 counteracted the inhibited cellular behaviors on account of AKIP1 interference. To be concluded, this study presented evidence that AKIP1 silencing suppressed the progression of glioma via targeting DLG2, which could provide novel insights to impede the development of glioma.

The Tianwen-1 Mars entry vehicle successfully landed on the surface of Mars in southern Utopia Planitia on May 15, 2021, at 7:18 (UTC+8). To acquire valuable Martian flight data, a scientific instrumentation package consisting of a flush air data system and a multilayer temperature-sensing system was installed aboard the entry vehicle. A combined approach was applied in the entry, descent, and landing trajectory reconstruction using all available data obtained by the inertial measurement unit and the flush air data system. An aerodynamic database covering the entire flight regime was generated using computational fluid dynamics methods to assist in the reconstruction process. A preliminary analysis of the trajectory reconstruction result, along with the atmosphere reconstruction and aerodynamic performance, was conducted. The results show that the trajectory agrees closely with the nominal trajectory and the wind-relative attitude. Suspected wind occurred at the end of the trajectory.

Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric disorders. However, the molecular and circuit mechanisms underlying the dysregulation remain elusive. Here, by using a mouse model of chronic social defeat stress (CSDS), we observed that the dysregulation varied drastically across individual projection neurons (PNs) in the basolateral amygdala (BLA), one of the kernel amygdala subregions critical for stress coping. While persistently reducing the extrasynaptic GABAA receptor (GABAAR)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus (BLA → vHPC PNs), CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis (BLA → adBNST PNs), suggesting projection-based dysregulation of tonic inhibition in BLA PNs by CSDS. Transcriptional and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss- and gain-of-function of δ-containing GABAARs (GABAA(δ)Rs) in BLA → vHPC and BLA → adBNST PNs, respectively. Importantly, it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS mice. Virally mediated maintenance of GABAA(δ)R currents in BLA → vHPC PNs occluded CSDS-induced anxiety-like behavior. These findings clarify the molecular substrate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology.

Throughfall (TF) is an important water input of rainfall redistribution into floor, and its spatial–temporal variability under some species' canopies has been documented to evaluate effect on splash erosion. However, the understanding of TF variability under large broad-leaved canopy remains insufficient. In this study, the spatial heterogeneity, temporal stability and drop size of TF were quantified using variogram fitting, normalised ranking and filter paper staining, respectively, under banana (Musa nana Lour.) canopy comprising long and wide leaves. Results indicated TF pattern showed strong spatial correlation at a range of 3–5 m. High spatial variability of TF was found, which was affected by rainfall event size and was accompanied by great canopy disturbance. TF plots revealed high time variability, which was mainly controlled by unstable banana canopy structure. TF drop size from leaf dripping points varied in 3–10 mm and showed significant differences (p < 0.05) among five kinds of leaf shapes, implying that concave and broken banana leaves were involved in the variability of TF drop size. Overall, results demonstrate the spatial–temporal variability of TF is dramatically induced by banana canopy with broad leaves, which may result in non-uniform soil water content and splash erosion under the canopy. HIGHLIGHTS The specific banana canopy notably modifies spatial-temporal variability of throughfall.; The spatial variability of throughfall was high and correlated with the rainfall event size.; The spatial pattern of throughfall showed low time stability based on multi-temporal levels.; Drop size of throughfall at different leaf shapes showed variable distribution in 3–10 mm.

Abdominal aortic aneurysm (AAA) has been associated with the dysfunction of vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM) remodelling. Runt-related transcription factor 3 (RUNX3) has been reported to be up-regulated in aneurysmal aorta samples compared with normal aorta. However, its function in VSMCs and the mechanism of function remains unknown. Therefore, our study aimed to investigate the role of RUNX3 in ECM remodelling and VSMC function, and further explore the underlying mechanism. Our results verified that RUNX3 was increased in aortic samples of AAA compared with healthy controls. Overexpression vectors of RUNX3 (ov-RUNX3) and siRNA of RUNX3 (si-RUNX3) were transfected into Human aortic smooth muscle cells (HAoSMCs). The results indicated that ov-RUNX3 promoted cell proliferation, migration, and MMP-2/3/9 secretion, and suppressed TIMP-1, collagen I/III, SM22, MYH11 and CNN1 expression in HAoSMCs. The silencing of RUNX3 has the opposite effect. Furthermore, we found that RUNX3 targets TGF-β1 and suppressed its transcription. The silencing of TGF-β1 increased cell proliferation, migration and MMP-2/3/9 expression, and inhibited TIMP-1, Collagen I/III, SM22, MYH11 and CNN1 expression. In addition, TGF-β1 reversed the effect of RUNX3 overexpression on HAoSMCs. Hence, our study indicated that RUNX3 promotes cell proliferation, migration, and ECM remodelling through suppressing TGF-β1.

Lipotoxicity has been implicated in the pathogenesis of obesity-related kidney damage and propagates chronic kidney injury like diabetic kidney disease; however, the underlying mechanisms have not yet been fully elucidated. To date, reduction of lipid acquisition and enhancement of lipid metabolism are the major, albeit non-specific, approaches to improve lipotoxic kidney damage. In the kidneys of high-fat diet (HFD)-fed mice and tubule cells cultured with palmitic acid (PA), we observed a dramatic upregulation of the long intergenic non-coding RNA-p21 (LincRNA-p21) through a p53-dependent mechanism. Kidney tubule cell-specific deletion of LincRNA-p21 attenuated oxidative stress, inflammation, apoptosis, and endoplasmic reticulum stress, leading to reduction of histological and functional kidney injury despite persistent obesity and hyperlipidemia. Mechanistically, HFD- or PA-initiated lipotoxicity suppressed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR)/murine double minute 2 homolog (MDM2) signaling cascade to activate p53 and enhance the transcriptional activity of LincRNA-p21. Collectively, our findings suggest that the p53/LincRNA-p21 axis is the downstream effector in lipotoxic kidney injury and that targeting this axis particularly in the kidney tubule could be a novel therapeutic strategy., Graphical abstract, Our study observed a dramatic upregulation of LincRNA-p21 through a p53-dependent mechanism in kidney tubule cells exposed to palmitic acid. Tubule cell-specific deletion of LincRNA-p21 prevented histological and functional kidney injury induced by high-fat diet. These findings suggest p53/LincRNA-p21 signaling axis as a potential therapeutic target for lipotoxic kidney injury.

A new species of freshwater crab of the genus Nanhaipotamon Bott, 1968 is described from Xiaye Village, Chengxiang Town, Longhai County, Zhangzhou City, Fujian Province, China. The new species is distinguished from congeners by the combination of characters of its carapace, third maxilliped, unequal chelipeds, triangular male abdomen and unique male first gonopod. Molecular evidence derived from partial mitochondrial 16S rRNA and COI genes also support the species as new.

AIM:To evaluate the clinical effect of 25G pars plana vitrectomy(PPV)combined with intraocular lens(IOL)ciliary sulcus suture fixation and replacement of IOL capsular bag complex.METHODS: A retrospective analysis of 21 patients(21 eyes)in our hospital who applied 25G PPV combined with IOL ciliary sulcus suture and fixation replacement in our hospital from January 2015 to January 2020 to treat the IOL capsular complex completely detached from the clinical data.RESULTS: All the cases were successfully removed the dislocated IOL complex during the operation. There was no iatrogenic retinal damage. During the operation, 4 cases(4 eyes)were found to have the retina hole, 2 cases(2 eyes)were found to be retinal lattice degeneration area, which were treated with laser photocoagulation of the retina. Follow-up for 6-18mo, best corrected visual acuity(BCVA)(LogMAR)increased from 0.40±0.30 before operation to 0.33±0.25 after operation(P=0.040). The BCVA at the last follow-up of all cases reached the BCVA before surgery. The absolute value of the difference between the postoperative spherical equivalent power and the preoperative IOL refractive power prediction value is less than or equal to 0.75D. At the last follow-up, the position of the intraocular lenses in all cases was good, and there were no complications such as retinal detachment. CONCLUSION: The technique of 25G PPV and the exchange of IOL ciliary sulcus fixation with intraocular IOL capsule complex is a safe and effective procedure for dislocation of IOL-capsular bag complex entirely into the vitreous cavity.

BackgroundWhole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.

Moyamoya disease (MMD) is an occlusive, chronic cerebrovascular disease affected by genetic mutation and the immune response. Furthermore, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) participate in the neointima of MMD, but the etiology and pathophysiological changes in MMD vessels remain largely unknown. Therefore, we established the circZXDC (ZXD family zinc finger C)–miR-125a-3p–ABCC6 (ATP-binding cassette subfamily C member 6) axis from public datasets and online tools based on “sponge-like” interaction mechanisms to investigate its possible role in VSMCs. The results from a series of in vitro experiments, such as dual luciferase reporter assays, cell transfection, CCK-8 assays, Transwell assays, and Western blotting, indicate a higher level of circZXDC in the MMD plasma, especially in those MMD patients with the RNF213 mutation. Moreover, circZXDC overexpression results in a VSMC phenotype switching toward a synthetic status, with increased proliferation and migration activity. CircZXDC sponges miR-125a-3p to increase ABCC6 expression, which induces ERS (endoplasmic reticulum stress), and subsequently regulates VSMC transdifferentiation from the contractive phenotype to the synthetic phenotype, contributing to the intima thickness of MMD vessels. Our findings provide insight into the pathophysiological mechanisms of MMD and indicate that the circZXDC–miR-125a-3p–ABCC6 axis plays a pivotal role in the progression of MMD. Furthermore, circZXDC might be a diagnostic biomarker and an ABCC6-specific inhibitor and has the potential to become a promising therapeutic option for MMD.

Identifying relatives across cohorts makes one of the basic routines for genomic data. As conventional such practice often requires explicit genomic data sharing, it is easily hampered by privacy or ethical constraints. In this study, using our proposed scheme for genomic encryption we developedencG-reg, a regression approach that is able to detect relatives of various degrees based on encrypted genomic data. The encryption properties ofencG-regis built on random matrix theory, which masks the original genotypic matrix but still provides controllable precision to that of direct individual-level genotype data. After having found tractable eighth-order moments for encrypted genotype, we established connection between the dimension of a random matrix and the required precision of a study.encG-regconsequently led to balanced i) false positive and false negative rates and ii) the computational cost and the degree of relatives to be searched. We validatedencG-regin 485,158 UKBiobank multi-ethnical samples, and the resolution ofencG-regwas comparable with the conventional method such as KING. In a more complex application, we launched a fine-devised multi-center collaboration across 6 research institutes in China, covering 11 cohorts of 64,091 GWAS samples. In both examples,encG-regrobustly identified and validated relatives existing across the cohorts even under various ethnical background and different genotypic qualities.

AIM: To explore the effect and safety of pars plana vitrectomy(PPV)assisted by intravitreal injection of conbercept in the treatment of proliferative diabetic retinopathy(PDR)combined with vitreous hemorrhage(VH).METHODS: In the prospective randomized controlled study, patients with PDR and VH who were admitted to ophthalmology department of the hospital from February 2017 to September 2019 were enrolled as the research objects. They were randomly divided into observation group(39 cases, 39 eyes)and control group(38 cases, 38 eyes). Both groups underwent standard 27G PPV. The observation group underwent intravitreal injection of conbercept within 6-7d before surgery. The perioperative indexes were collected. The best corrected visual acuity(BCVA), intraocular pressure and central macular thickness(CMT)were followed up. The occurrence of surgical related complications was statistically analyzed.RESULTS: Operation time(74.18±15.26 vs 96.17±14.27min), number of bleeding eyes(8% vs 37%), ratio of silicone oil filling(18% vs 53%)and incidence of iatrogenic retinal breaks(15% vs 47%)were lower in observation than control group(P0.05).CONCLUSION: For patients with PDR and VH, intravitreal injection of conbercept before PPV can shorten operation time, reduce intraoperative blood loss and alleviate macular edema to obtain better visual acuity, with better curative effect and safety.

To enhance the performance of metal-polymer joint, surface modification is normally applied. Different from the common methods of increasing roughness or manufacturing complicated patterning, a new strategy of microscale morphology design of low roughness surface was introduced in this work, for improving the interfacial bonding strength between Ti6Al4V titanium alloy (TC4) and polyethylene terephthalate (PET) joined by hot pressing method. Low-roughness (Ra = 0.18 μm) surface achieved by HF etching can also significantly enhance the interfacial bonding strength of TC4-PET joint by 133%, from 4.5 MPa (as-polished) to 10.5 MPa, as high as the joint strength achieved by sandblasting (11 MPa) with much higher roughness (Ra = 3.7 μm). The bonding mechanisms in joints with different surface treatments were investigated and compared, showing that a new effect of surface particle anchoring played a key role in enhancing the interfacial bonding. Based on the characterization results and analyses, the crack propagation paths of HF and HNO3-HF treated samples were clarified and illustrated. This study indicated that roughness is not the only decisive factor of joint strength and demonstrated a new effective strategy via synergistic effects of surface particle anchoring and chemical bonding to improve interfacial bonding of metal and polymer from both theoretical and practical points of view.

Designing MOF-based materials with desired electrochemical activity and high electron conductivity may yield a novel electrochemical sensor that effectively detects various organic pollutants and conducts health monitoring. This study developed a facile and versatile electrochemical sensor for simultaneously monitoring the environmental pollutants hydroquinone (HQ) and catechol (CT). The electrodes are fabricated by modifying a GCE with a Cu-functionalized MOF (UiO-bpydc-Cu) and multi-walled carbon nanotubes (MWCNTs). The Cu-functionalized MOF effectively improved the electronic conductivity by metalating the 2,2'-bipyridyl-derived UiO-bpydc with Cu

Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS.