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By increasing d-band electrons and the conductivity via electron-donating S-doping, the Fe–SN–C single-atom catalyst exhibits high efficiency for CO2 electroreduction reaction.

Adaptive radiotherapy (ART) is a new radiotherapy technology based on image-guided radiation therapy technology, used to avoid radiation overexposure to residual tumors and the surrounding normal tissues. Tumors undergoing the same radiation doses and modes can occur unequal shrinkage due to the variation of response times to radiation doses in different patients. To perform ART effectively, eligible patients with a high probability of benefits from ART need to be identified. Confirming the precise timetable for ART in every patient is another urgent problem to be resolved. Moreover, the outcomes of ART are different depending on the various image guidance used. This review discusses 'who, when and how' as the three key factors involved in the most effective implementation for the management of ART.Adaptive radiotherapy (ART) is an image-guided radiotherapy technology used to treat tumors. This article explores who can gain more benefits from ART, when is the optimal time to conduct ART and how to better implement ART. Non-small-cell lung cancer patients with large tumor lesions and high radiosensitivity are the most suitable people for ART. The period of 30–50 Gy and 15–25 fractions of radiotherapy may be the most appropriate time for ART. All imaging guidances have their advantages and disadvantages. Although ART has more benefits, ART is not universally used in the clinic because of the associated labor, economic burden and need for equipment updating. This paper helps guide and popularize the application of the ART strategy in the clinic within economic benefits and feasibility.

A significant proportion of incident and prevalent hemodialysis patients have central venous catheters for vascular access. No consensus is available on the prevention of catheter dysfunction or catheter-related bloodstream infections in patients undergoing hemodialysis by means of catheter lock solutions.We reviewed the effects of single and combined anticoagulants with antibacterial catheter lock solutions or other antimicrobials for the prevention of thrombosis or infections in hemodialysis patients. Relative risks with 95% confidence intervals for trials of the same type of catheter locking solution were pooled.We included original research articles in English from PubMed, EMBASE, SpringerLink, Elsevier and Ovid using the search terms 'hemodialysis,' 'central venous catheter,' 'locking solution,' 'UFH,' 'low molecular weight heparin,' 'EDTA,' 'citrate,' 'rt-PA,' 'urokinase,' 'gentamicin,' 'vancomycin', 'taurolidine,' 'sodium bicarbonate,' 'hypertonic saline' and 'ethanol' and 'catheter'.Low-dose heparin lock solution (5000 U/ml) can efficiently achieve anticoagulation and will not increase the risk of bleeding. Low-concentration citrate (5%) combined with rt-PA can effectively prevent catheter infection and dysfunction. Catheter-related infections may be minimized by choosing the appropriate antibiotic and dose.There is a lack of follow-up validation data for LMWH, EDTA, taurolidine, sodium bicarbonate, ethanol, and other lock solutions.Since catheterization is common in hemodialysis units, studies on long-term treatment and preventative strategies for catheter dysfunction and catheter-related infection are warranted.

Background Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-β1 (TGF-β1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. Methods Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRβ + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-β1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. Results An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-β1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-β1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. Conclusions The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

Background This study aimed to develop and validate an easy-to-use ICU illness scoring system to evaluate the in-hospital mortality for very old patients (VOPs, over 80 years old). Methods We performed a multicenter retrospective study based on the eICU Collaborative Research Database (eICU-CRD), Medical Information Mart for Intensive Care Database (MIMIC-III CareVue and MIMIC-IV), and the Amsterdam University Medical Centers Database (AmsterdamUMCdb). Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to variables selection. The Logistic regression (LR) algorithm was used to develop the risk score and a nomogram was further generated to explain the score. Results We analyzed 23,704 VOPs, including 3,726 deaths (10,183 [13.5% mortality] from eICU-CRD (development set), 12,703 [17.2%] from the MIMIC and 818 [20.8%] from the AmsterdamUMC (external validation sets)). Thirty-four variables were extracted on the first day of ICU admission, and 10 variables were finally chosen including Glasgow Coma Scale, shock index, respiratory rate, partial pressure of carbon dioxide, lactate, mechanical ventilation (yes vs. no), oxygen saturation, Charlson Comorbidity Index, blood urea nitrogen and urine output. The nomogram was developed based on the ten variables (AUC: training of 0.792, testing of 0.788, MIMIC of 0.764 and AmsterdamUMC of 0.808 [external validating]), which consistently outperformed the SOFA, APS-III, and SAPS-II. Conclusions We developed and externally validated a nomogram for predicting mortality in VOPs based on 10 commonly measured variables on the first day of ICU admission. It could be a useful tool for clinicians to identify potentially high risks of VOPs.

The present study investigates the diachronic development of the bipartite negative construction hǎa…mây in Thai, aiming to account for its syntactic and semantic peculiarity. Based on the historical data from the Sukhothai period to Modern Thai, I suggest that the development of hǎa…mây construction relates to the grammaticalization of the expression hǎa NP míɁ dây ‘fail to find something’. From around the mid-14th century, hǎa NP míɁ dây came to gain a new function as an irregular negative existential construction under the pressure of the recession of the anterior negative existential form bɔ̀ɔ mii ‘not have, not exist’. This function is especially prominent in the 17th century during which the old negator bɔ̀ɔ shows a continuous decrease in the frequency of use and the newer negator mây was not widely used. When the newer negative existential form mây mii emerged around the early 18th century and eventually prevailed over hǎa NP míɁ dây in the 19th and 20th centuries, hǎa NP míɁ dây gradually lost its function as a negative existential form but survived its evolution into a negative adverbial construction through a syntagmatic change (from hǎa NP to hǎa VP), accompanied by a phonetic reduction (from hǎa…míɁ dây to hǎa…mây ) and a semantic reinterpretation(from ‘fail to find something or not exist, not have’ to ‘not VP as one thought’).

Introduction: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient’s quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. Methods: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3–6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score. Results: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. Conclusion: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

The two-dimensional magnetic lattice of Gd3Cu9(OH)19Br8, where Gd3+ ions are located in the center of hexagonal holes of the Cu-Kagome lattice.

Spin-gapless semiconductor (SGS) materials are regarded as the most promising candidates for ideal massless and dissipationless states towards low-power spintronic device applications. Here, we propose a spin-gapless semiconducting black arsenic-phosphorus (AsP) monolayer halogenated by chlorine (Cl) adatoms and reveal the perfect spin Seebeck effect induced by its SGS character to produce pure thermal spin-current using first-principles calculations. Our results show that Cl atoms prefer to adsorb P atoms rather than As atoms in the AsP monolayer, behaving as a ferromagnetic semiconductor. The As-adsorbed AsP monolayer as an ideal SGS material with parabolic-type energy dispersion can be utilized to realize symmetrical spin Seebeck current for perfect pure thermal spin-current even at an extremely low on-off temperature. Moreover, in-plane strain engineering can effectively manipulate the electronic structures of the P-absorbed AsP monolayer for perfect parabolic-type SGS similar to As-adsorbed AsP, and to obtain the relevant thermoelectric effect. These distinct features suggest the potential applications of the Cl-halogenated AsP monolayer with the SGS character in low-power spin-caloritronic devices.

Background: IgA nephropathy is the most common primary glomerular disease and an important cause of chronic kidney disease. Previous clinical studies have confirmed that Huangkui capsule could reduce urine protein of IgA nephropathy by 100 mg/d losartan potassium. However,the effect of Huangkui capsule on IgA nephropathy is not clear. Methods: Based on two multicenter, large sample phase IV clinical trials (NCT 02231125; NCT 02231138), eligible IgA nephropathy patients were screened and the related data were extracted for secondary analysis. Patients were grouped according to the baseline urinary protein, glomerular filtration rate, or pathologic characteristics using IgA nephropathy Oxford classification and the curative effect was analyzed. Taking the decrease of urine protein ≥30% after Huangkui capsule 6-month treatment as the effective standard, multiple regression analysis was used to analyze the influencing factors of Huangkui capsule in reducing urinary protein in IgA nephropathy patients. Results: 503 patients with IgA nephropathy were enrolled. The efficacy of Huangkui capsule in reducing urinary protein in patients with baseline 24h urinary protein ≥1.0 g/d or glomerular filtration rate ≥60 ml/min reach the effective standard. 24h baseline urinary protein, body mass index, serum albumin, and serum creatinine were the independent influencing factors of Huangkui capsule in reducing urinary protein, but there was no significant correlation with the baseline pathological characteristics. After 6 months of Huangkui capsule treatment, the decrease rate of urine protein increased by 7.9% for every 100mg increase of 24h urinary protein and 6.7% for every 1g/L increase of ALB, while decreased by 1.1% and 7% respectively, for every 1μmmol/L increase of serum creatinine and 1kg/m2 increase of body mass index. Conclusion: The effect of Huangkui capsule is influenced by basic urinary protein, body mass index, serum albumin, and serum creatinine in IgA nephropathy patients. Huangkui capsule can effectively reduce urinary protein in patients with baseline urinary protein ≥1.0 g/d or glomerular filtration rate ≥60 ml/min.

Introduction: Youthful blood environment was shown to decelerate the aging process of kidney and to attenuate senile renal fibrosis in a young-old parabiotic animal model; in addition, we identified a stem cell factor (SCF) that is closely linked with the process. This research was to investigate the effect of youthful blood environment on senile renal interstitial fibrosis and the role of SCF. Methods: We bred SCF receptor c-Kit gene loss-of-function Wps/Wps mice and established a combination mice model that was subjected to unilateral ureteral obstructive (UUO) and parabiotic surgeries. Parabiotic mice were divided into isochronic parabiotic (young-young, Y-IP and old-old, O-IP) and heterochronic parabiotic (young-old, HP) groups. UUO surgery was performed in one of the parabiotic pairs in the IP group (Y-IPuuo and O-IPuuo) and in the elderly mice in the HP group (O-HPuuo). In order to study the role of SCF/c-kit on renal interstitial fibrosis, UUO surgery was performed in wildtype (WT) and Wps/Wps mice. Results: Fourteen days after UUO surgery, the kidney interstitial fibrosis area, kidney function, and the expressions of SCF/c-Kit, pNF-κB, and fibrosis-related proteins in the O-HPuuo group were significantly lower than those in the Ouuo and O-IPuuo groups. Compared with wildtype UUO mice, the expressions of pNF-κB and fibrosis-related proteins, and the kidney function were all significantly decreased in Wps/Wps UUO mice. Conclusion: Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice, and ameliorated UUO-induced kidney fibrosis and function loss.

Due to the rapid mutation of porcine epidemic diarrhea virus (PEDV), existing vaccines cannot provide sufficient immune protection for pigs. Therefore, it is urgent to design the affinity peptides for the prevention and control of this disease. In this study, we made use of a molecular docking technology for virtual screening of affinity peptides that specifically recognized the PEDV S1 C-terminal domain (CTD) protein for the first time. Experimentally, the affinity, cross-reactivity and sensitivity of the peptides were identified by an enzyme-linked immunosorbent assay (ELISA) and a surface plasmon resonance (SPR) test, separately. Subsequently, Cell Counting Kit-8 (CCK-8), quantitative real-time PCR (qRT-PCR), Western blot and indirect immunofluorescence were used to further study the antiviral effect of different concentrations of peptide 110766 in PEDV. Our results showed that the P/N value of peptide 110766 at 450 nm reached 167, with a KD value of 216 nM. The cytotoxic test indicated that peptide 110766 was not toxic to vero cells. Results of the absolute quantitative PCR revealed that different concentrations (3.125 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM, 200 μM) of peptide 110766 could significantly reduce the viral load of PEDV compared with the virus group (p < 0.0001). Similarly, results of Western blot and indirect immunofluorescence also suggested that the antiviral effect of peptide 110766 at 3.125 is still significant. Based on the above research, high-affinity peptide 110766 binding to the PEDV S1-CTD protein was attained by a molecular docking technology. Therefore, designing, screening, and identifying affinity peptides can provide a new method for the development of antiviral drugs for PEDV.

IntroductionTo explore the CT characteristics for the prediction of long term survival in gastric cancer patients with synchronous peritoneal metastasis (PM).Materials and methodsSixty-six patients diagnosed as gastric cancer with synchronous peritoneum metastasis were enrolled in this retrospective study. Ten anatomic peritoneal regions were evaluated to check for the signs of PM on CT. One positive area equaled one score. The CT characteristic-based PM score (CT-PMS) was the sum of the total points assigned to all 10 regions, with a range of 0–10. The triple tract dilatation (TTD) sign caused by peritoneal metastasis, the presence of extensive lymph node metastasis (ELM), and the grade of ascites were recorded. The overall survival (OS) was used as the prognostic indicator. The performance of the CT characteristics was assessed by the Kaplan–Meier analysis and Cox proportional hazards model, while its reproducibility was evaluated by Kappa statistic and weighted Kappa statistic.ResultsPatients with a CT-PMS of 3–10 had significantly poorer OS (P = .02). Patients with either the presence of TTD sign, or ELM had a trend toward unfavorable OS (both P = .07), and when CT-PMS of 3–10 was detected simultaneously, the survival was further reduced (P = .00 for TTD sign; P = .01 for ELM). The grade of ascites failed to show a significant correlation with OS. The interobserver reproducibility for assessing the CT-PMS, the presence of TTD sign, the presence of ELM, and the grade of ascites had a substantial to almost perfect agreement.ConclusionThe prognosis of gastric cancer patients with PM has a correlation with the extent of metastasis dissemination on baseline CT. A CT-PMS of 3–10 is associated with a worse prognosis than that of 0–2. The presence of TTD sign and ELM may help further select patients with extraordinarily poor prognoses.

Gram-positive enhancer matrix (GEM) nanoparticles are often used in mucosal immunity, preparation of subunit vaccines or as an immune adjuvant due to its good immunological activities in recent years. Here, we designed and screened out a high affinity peptide ligand PL23, which could specifically target the non-epitope region of Classic Swine Fever Virus (CSFV) E2 protein, by virtual screening technology, enzyme linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) test. The OD value of PL23 at 450 nm was reached 1.982, and the KD value of it was 90.12 nM. Its binding capacity to protein was verified by SDS-PAGE as well. PL23 was subsequently conjugated to GEM nanoparticles by dehydration synthesis generating GEM-PL23 particles, and the GEM-PL-E2 particles were assembled after incubated with CSFV E2 protein. The cytotoxic test indicated that PL23, CSFV E2 protein, GEM nanoparticles, GEM-PL23 particles and GEM-PL-E2 particles were not toxic to cells and GEM nanoparticles could significantly promote the growth of APCs at high concentration for 1 h, p

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, and its early pathogenesis is critical. Shear stress caused by glomerular hyperfiltration contributes to the initiation of kidney injury in diabetes. The primary cilium of renal tubular epithelial cells (RTECs) is an important mechanical force sensor of shear stress and regulates energy metabolism homeostasis in RTECs to ensure energy supply for reabsorption functions, but little is known about the alterations in the renal cilium number and length during the progression of DKD. Here, we demonstrate that aberrant ciliogenesis and dramatic increase in the cilium length, the number of ciliated cells, and the length of cilia are positively correlated with the DKD class in the kidney biopsies of DKD patients by super-resolution imaging and appropriate statical analysis methods. This finding was further confirmed in STZ-induced or db/db diabetic mice. These results suggest that the number and length of renal cilia may be clinically relevant indicators and that cilia will be attractive therapeutic targets for DKD.

Biological age (BA) may reflect the actual aging state in humans better than chronological age (CA). The study aimed to construct BA models suitable for the Chinese Han population by selecting appropriate aging markers and evaluation methods.A total of 1207 individuals (21∼91 years) from the Han Chinese population in Beijing were examined for essential organ functions, and 156 cardiovascular, pulmonary function, and atherosclerotic indices and clinical and genetic factors were used as candidate markers of aging. BA models were constructed using multiple linear regression (MLR), principal component analysis (PCA), and the Klemera and Doubal method (KDM). Models were internally and externally validated using cross-validation and disease populations.Nine aging markers were selected. Two MLR, three PCA, and three KDM models were successfully constructed. External validation showed that the difference between CA and BA was most significant in the PCA3 and KDM2 models, while there was no significant difference in the MLR1 and MLR2 models; the fitted lines for BA in the disease population were higher than those in the healthy population in the MLR1, MLR2, KDM1, and KDM2 models, while the other models showed the opposite.Based on a healthy population in Beijing, nine markers representing multiple organ/system functions were screened from the candidate markers, eight methods were successfully used to construct BA models, and the KDM2 model was found to potentially be more appropriate for assessing BA in the Chinese Han population.

The relationship between transforming growth factor β superfamily members (GDF11 and BMP4) and bone metabolism remains controversial. The aim of this study was to investigate the association between serum GDF11 and BMP4 levels and lumbar spine bone mineral density (LBMD) in a cohort of postmenopausal Chinese women. This was a non-prospective cross-sectional study of 350 postmenopausal women with a mean age of 63.13 ± 8.66 years who came from Shenyang, China. LBMD was measured using dual-energy X-ray absorptiometry. Serum GDF11 and BMP4 concentrations were detected using a sandwich enzyme immunoassay kit. Pearson’s correlation analysis and regression analyses were carried out to investigate the relationships between LBMD and serum GDF11 and BMP4 levels. A linear association between LBMD and serum LgGDF11 concentration was observed after adjusting for numerous confounders (P = 0.018). In addition, the osteoporosis (OP) was inversely related to LgGDF11 and the odds ratios for postmenopausal women with lumbar OP in LgGDF11 quartile group 2, group 3, and group 4 were 0.46 (95% CI 0.23–0.90, P

Alpha gliadin peptide induces damage and apoptosis of intestinal cells and aggravates pathology of celiac disease (CD) by inducing oxidative stress. Therefore, inhibition or alleviation of oxidative stress in CD may be an effective approach to the adjunctive treatment of CD. Black soybean peptides (BSPs) have been shown to inhibit oxidative stress and inflammation. The effect of BSPs on CD remains unknown. In this paper, the effect and mechanism of BSPs on the α-gliadin peptide (p31-43)-induced Caco-2 cytotoxicity were studied. We identified BSPs that alleviated the cytotoxicity of p31-43 in the CD cell model: Caco-2 cells were pre-treated with bioactive peptides for 3 hours before the addition of p31-43 for treatment for 24 hours, and then cells were collected for subsequent experiments. Our results show that p31-43 can significantly increase the ROS and MDA levels of Caco-2 cells, disrupt the glutathione redox cycle, reduce the activity of the antioxidant enzyme, and inhibit the activation of antioxidant signaling pathways. BSPs pretreatment can inhibit the increase of Keap1 protein induced by p31-43, activate antioxidant genes through Nrf2 protein, improve the activity of the antioxidant enzyme, alleviates glutathione redox cycle imbalance, promote the expression of GCLC or GCLM, and reduce oxidative damage.Graphical AbstractPattern of BSPs against oxidative damage in CD cell mode.

With the continuous development of China’s economy and society, people and the government have higher and higher requirements for food safety. Testing for food dopants and toxins can prevent the occurrence of various adverse health phenomena in the world’s population. By deploying new and powerful sensors that enable rapid sensing processes, the food industry can help detect trace adulteration and toxic substances. At present, as a common food safety detection method, lateral flow immunochromatography (LFI) is widely used in food safety testing, environmental testing and clinical medical treatment because of its advantages of simplicity, speed, specificity and low cost, and plays a pivotal role in ensuring food safety. This paper mainly focuses on the application of lateral flow immunochromatography and new technologies combined with test strips in food safety detection, such as aptamers, surface-enhanced Raman spectroscopy, quantum dots, electrochemical test strip detection technology, biosensor test strip detection, etc. In addition, sensing principles such as fluorescence resonance energy transfer can also more effective. Different methods have different characteristics. The following is a review of the application of these technologies in food safety detection.

Antigen proteins, assembled on nanoparticles, can be recognized by antigen-presenting cells effectively to enhance antigen immunogenicity. The ability to simultaneously display multiantigens on the same nanoparticle could have numerous applications but remained technical challenges. Here, we described a method for precise assembly of multiple antigens on nanoparticles with specially designed affinity peptides. First, we designed and screened affinity peptides with high affinity and specificity, which could respectively target the key amino acid residues of classical swine fever virus (CSFV) E2 protein or porcine circovirus type 2 capsid protein (PCV2 Cap) accurately. Then, we conjugated the antigen proteins to poly(lactic acid-glycolic acid) copolymer (PLGA) and Gram-positive enhancer matrix (GEM) nanoparticles through the peptides and perfectly assembled two kinds of multiantigen display nanoparticles with different particle sizes. Subsequently, the immunological properties of the assembled nanoparticles were tested. The results showed that the antigen display nanoparticles could promote the maturation, phagocytosis, and proinflammatory effects of antigen-presenting cells (APCs). Besides, compared with the antigen proteins, multiantigen display nanoparticles could induce much higher levels of antibodies and neutralizing antibodies in mice. This strategy may provide a technical support for the study of protein structure and the research and development of polyvalent vaccines.

The primary cilium is a hair-like, microtubule-based organelle that is covered by the cell membrane and extends from the surface of most vertebrate cells. It detects and translates extracellular signals to direct various cellular signaling pathways to maintain homeostasis. It is mainly distributed in the proximal and distal tubules and collecting ducts in the kidney. Specific signaling transduction proteins localize to primary cilia. Defects in cilia structure and function lead to a class of diseases termed ciliopathies. The proper functioning of primary cilia is essential to kidney organogenesis and the maintenance of epithelial cell differentiation and proliferation. Persistent cilia dysfunction has a role in the early stages and progression of renal diseases, such as cystogenesis and acute tubular necrosis (ATN). In this review, we focus on the central role of cilia in kidney development and illustrate how defects in cilia are associated with renal disease progression.

Immunotherapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have revolutionized the treatment of patients with advanced and metastatic tumors resistant to traditional therapies. However, the immunosuppressed tumor microenvironment (TME) results in a weak response to immunotherapy. Therefore, to realize the full potential of immunotherapy and obstacle barriers, it is essential to explore how to convert cold TME to hot TME. Autophagy is a crucial cellular process that preserves cellular stability in the cellular components of the TME, contributing to the characterization of the immunosuppressive TME. Targeted autophagy ignites immunosuppressive TME by influencing antigen release, antigen presentation, antigen recognition, and immune cell trafficking, thereby enhancing the effectiveness of cancer immunotherapy and overcoming resistance to immunotherapy. In this review, we summarize the characteristics and components of TME, explore the mechanisms and functions of autophagy in the characterization and regulation of TME, and discuss autophagy-based therapies as adjuvant enhancers of immunotherapy to improve the effectiveness of immunotherapy.

A new triangular lattice compound Gd

PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and MethodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Lung cancer ranking high in the cancer-related list has long perplexed patients, in which glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is found to be highly expressed. Besides, DNA methylation is perceived as a biomarker to assess the prognosis of patients with various cancers. However, the correlation between GNPNAT1 and DNA methylation and the role of GNPNAT1 in lung cancer remain vague.Principal component analysis (PCA), heatmap, volcano map, Venn diagram, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to screen out the candidate genes. The viability, migration, and invasion of lung cancer cells were detected by CCK-8 and Transwell assays. An xenograft tumor mouse model was established. The relative expressions of GNPNAT1, E-cadherin, vimentin, Matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), E2F1, and cyclin D1 in cells or xenograft tumor tissues were quantified by Western blot, RT-qPCR, or immunohistochemistry assay.GNPNAT1 was screened as the research object. GNPNAT1 methylation was downregulated, while GNPNAT1 expression was upregulated in lung cancer tissues. The methylation and mRNA levels of GNPNAT1 were correlated with the patient prognosis. GNPNAT1 increased cell viability, migration and invasion, and promoted the xenograft tumor volume and weight, whereas shGNPNAT1 acted oppositely. Moreover, expressions of Vimentin, MMP-2, E2F1, and cyclin D1 were increased, but E-cadherin and TIMP-2 expressions were decreased by overexpressed GNPNAT1, whilst GNPNAT1 knockdown ran conversely.GNPNAT1 and methylated GNPNAT1 coverage are biomarkers for the diagnosis and prognosis of lung cancer.

Sites dated to the early late Pleistocene are still limited in North China, which has hindered the detailed analysis of the development of Paleolithic industries in the late Pleistocene in this area. The Youfangbei (YFB) site is a newly excavated small-flake-tool Paleolithic site near the Youfang (YF) microblade site in the Nihewan Basin, North China. Because the small-flake-tool industry still existed in the late part of the late Pleistocene and might be related to the emergence of microlithic industries, the relationship between the two sites needs to be determined through a chronological study. Two profiles were excavated, and most of the artifact assemblages were unearthed in the lower profile (T1) from a depth of 0.9 m from the bottom. In this study, the feldspar post-infrared infrared stimulated luminescence method was applied to determine the age of the YFB site. Results showed that the upper profile was deposited from 86–0.5 ka, and the cultural layer in T1 yielded age of 124–82 ka, corresponding to Marine Isotope Stage (MIS) 5, with an irregular but generally mild climate. The age of the YFB site is too old to be directly related to that of the YF site, but it partly bridges a chronological gap of human occupation in the Nihewan Basin.

Confocal microscopy is one of the most widely used tools for high-resolution cellular, tissue imaging and industrial inspection. Micrograph reconstruction based on deep learning has become an effective tool for modern microscopy imaging techniques. While most deep learning methods neglect the imaging process mechanism, which requires a lot of work to solve the multi-scale image pairs aliasing problem. We show that these limitations can be mitigated via an image degradation model based on Richards-Wolf vectorial diffraction integral and confocal imaging theory. The low-resolution images required for network training are generated by model degradation from their high-resolution counterparts, thereby eliminating the need for accurate image alignment. The image degradation model ensures the generalization and fidelity of the confocal images. By combining the residual neural network with a lightweight feature attention module with degradation model of confocal microscopy ensures high fidelity and generalization. Experiments on different measured data report that compared with the two deconvolution algorithms, non-negative least squares algorithm and Richardson-Lucy algorithm, the structural similarity index between the network output image and the real image reaches a high level above 0.82, and the peak signal-to-noise ratio can be improved by more than 0.6 dB. It also shows good applicability in different deep learning networks.

To determine the relevance of morphometric properties attributed to the meat yield and fatness index of the saltwater hard clam Meretrix meretrix. A new strain of M. meretrix with red shell color was produced after five generations of selection within a family of full-sibs. 7 morphometric traits, including shell length (SL), shell height (SH), shell width (SW), ligament length (LL), projection length (PL), projection width (PW), and live body weight (LW), and 2 meat characteristics, including meat yield (MY) and fatness index (FI) were measured from 50 individuals of three-year-old M. meretrix. The correlation coefficients, path coefficients, determination coefficients among attributes were analyzed. The results indicated that correlation achieved very significant levels (PR2) of morphometric traits against the meat yield and fatness index of clams were 0.901 and 0,929, respectively, indicating that the live body weight and shell length were the common main factors influencing the meat characteristics. By testing the significance of partial regression coefficient and gradually removing the non-significant morphometric traits, a multiple regression equation was established to estimate the relationship between shell length (SL, mm), live body weight (LW, g), ligament length (LL, mm) and meat yield (MY, %), fat index (FI, %): MY (%) = 0.432SL+0.251LW and FI (%) = 0.156SL+0.067LL+0.42LW-3.533. The study draws a conclusion that live body weight and shell length have a predominant direct effect on the meat yield and fatness index, which provides theoretical information for the breeding of M. meretrix.

BackgroundThe disease pathology for diabetes mellitus patients with chronic kidney disease (CKD) may be diabetic nephropathy (DN), non-diabetic renal disease (NDRD), or DN combined with NDRD. Considering that the prognosis and treatment of DN and NDRD differ, their differential diagnosis is of significance. Renal pathological biopsy is the gold standard for diagnosing DN and NDRD. However, it is invasive and cannot be implemented in many patients due to contraindications. This article constructed a new noninvasive evaluation model for differentiating DN and NDRD.MethodsWe retrospectively screened 1,030 patients with type 2 diabetes who has undergone kidney biopsy from January 2005 to March 2017 in a single center. Variables were ranked according to importance, and the machine learning methods (random forest, RF, and support vector machine, SVM) were then used to construct the model. The final model was validated with an external group (338 patients, April 2017–April 2019).ResultsIn total, 929 patients were assigned. Ten variables were selected for model development. The areas under the receiver operating characteristic curves (AUCROCs) for the RF and SVM methods were 0.953 and 0.947, respectively. Additionally, 329 patients were analyzed for external validation. The AUCROCs for the external validation of the RF and SVM methods were 0.920 and 0.911, respectively.ConclusionWe successfully constructed a predictive model for DN and NDRD using machine learning methods, which were better than our regression methods.Clinical Trial RegistrationClinicalTrial.gov, NCT03865914.

Acute kidney injury (AKI) is a global disease with high morbidity and mortality. At present, the treatment of AKI still lacks targeted measures. Ferroptosis, a form of regulated cell death, plays an essential role in the initiation and progression of AKI. Current evidence proves that targeting ferroptosis is supposed to be a novel potential strategy to cure AKI. In this study, we aim to use bibliometric analysis to identify research trends and hotspots in the field of "ferroptosis in AKI".We chose the Science Citation Index Expanded (SCI-EXPANDED) index of the Web of Science Core Collection (WoSCC) as the source database for data retrieval. Data were retrieved from the WoSCC on May 24, 2022. Full records and cited references of all the documents in WoSCC were collected. The R software and the Online Analysis Platform of Literature Metrology were used for data analysis and visual analysis.There were 120 documents on "ferroptosis in AKI" in the WOSCC from 2014 to 2022 (May 24, 2022). There was a clear upward trend each year in the number of documents published. According to WoS report, China, the United States, and Germany were the top three countries involved in this research area, the majority of publications were included in the subject area "Cell Biology". Technical University of Dresden contributed the most publications, followed by Central South University and University of Pittsburgh. The Journal of Cell Death and Disease had the highest H-index and contributed the most publications. Linkermann A authored 16 articles and had the highest H-index. Multifactorial analysis of the keywords show that the research field is divided into two clusters. The most contributing publications and the most cited publications were also determined by factorial analysis.This bibliometric analysis provides a comprehensive analysis of research trends and hot spots on the topic of "ferroptosis in AKI". The study of ferroptosis-related AKI research remains in its early stages. There will be a dramatically increasing number of publications on this field. Further research should focus on exploring the mechanisms of crosstalk between ferroptosis and other programmed cell deaths, and improves clinical applications and therapeutic effects against AKI.

Background Nontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab. Case presentation A middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up. Conclusion We reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

Along with the peritoneal dialysis (PD)-favored policy in China and the implementation of more comprehensive PD management, PD has evolved in Chinese mainland over the last decade. Despite the existence of national registries and several provincial epidemiological descriptive studies, there was almost no national research on the changing trajectory in PD population. A comparison study, based on two national surveys that were 10 years apart, was conducted to reveal the evolvement of PD care in Chinese mainland.Two national surveys have been done respectively in 2010 and 2020 to capture the epidemiological status, application of different modalities, management of perioperative infection, and long-term complications among PD patients.In the study with 730 participating hospitals (n = 14,912 PD patients) in 2010 and 746 hospitals (n = 101,537) in 2020, prevalent PD patients have increased in the past 10 years with increased numbers of PD patients in both secondary (average 5 ± 16 vs. 43 ± 41, p 0.01) and tertiary hospitals (32 ± 53 vs. 153 ± 215, p 0.01). Automated PD has been accessible in 0.4% of all hospitals, only in tertiary centers in 2010 and its application increased to 51% in 2020. PD centers have become more engaged in PD catheter placement, treated properly for the PD-related infection, and carried out the follow-up in compliance with the national protocols.Our study indicates that over the past decade, the prevalent PD population has quickly expanded with increased APD availability in Chinese mainland. The management of PD patients has become better conforming to the guidelines and long-term follow-up of patients have remained stable. Further studies are warranted to evaluate whether the rapidly changing paradigm of PD could translate into the socio-economic benefits in the society.

BACKGROUND Peritoneal dialysis (PD) care in mainland China has been progressing in the past 10 years. OBJECTIVE To complement information from the dialysis registry, a large-scale nationwide survey was conducted to investigate the current infrastructure and management of PD care at hospitals of different tiers. METHODS A web-based multiple-choice questionnaire was distributed through the National Center for Nephrology Medical Quality Management and Control to PD centers of secondary and tertiary hospitals in October 2020. The 2-part survey collected the information of PD centers and the clinical management of patients on PD. A total of 788 effective surveys from 746 hospitals were voluntarily returned, and data were extracted and analyzed. RESULTS The effective survey data covered 101,537 patients on PD, with 95% (96,460/101,537) in the tertiary hospitals. The median number of patients per PD center was 60 (IQR 21-152); this number was 32 (IQR 8-65) and 70 (IQR 27-192) for secondary and tertiary hospitals, respectively. There was a discrepancy in the availability of designated physical areas for different functions of PD care between the secondary and tertiary hospitals. The proportion of tertiary hospitals with PD training (P=.01), storage (P=.09), and procedure area (PPP CONCLUSIONS This national survey reflects the current status and disparities of PD center management in mainland China. The study results suggest that the PD care needs to be more conveniently accessible in secondary hospitals, and quality management and staff training in secondary hospitals are still in high demand.

Background End-stage renal disease patients with maintenance hemodialysis have high-mortality risk. The association of different age of hemodialysis patients with mortality remains uncertain in China. This study aimed to assess the survival outcomes and risk factors affecting mortality between young and elderly patients with maintenance hemodialysis.Methods The multicenter retrospective cohort study enrolled adult patients undergoing maintenance hemodialysis from 24 hemodialysis centers in China between January 1, 2008, and September 30, 2015. The patients were assigned to young and elderly group according to age on the initiation of the hemodialysis. The primary outcome was all-cause mortality of patients. Survival outcomes of patients was performed using a Kaplan-Meier survival analysis. Multivariate cox proportional hazards regression models were implemented to identify risk factors affecting all-cause mortality of patients with maintenance hemodialysis.Results A total of enrolled 1601 patients undergoing maintenance hemodialysis, including 642 young patients and 959 elderly patients. The mean follow-up duration was 48.17 ± 25.59 months, the all-cause mortality was 64 (9.97%) in young group and 255 (26.59%) in elderly group, the hazard ratio [HR] of elderly patients relative to young patients, 1.699 (95% confidence interval [95% CI], 1.482 to 1.949, P＜0.001). The Kaplan-Meier survival curve showed that overall cumulative survival was lower in elderly group than young group (Log Rank tests = 63.31, P＜ 0.001). Multivariate cox regression analysis revealed that the cardiovascular disease (HR, 1.544; 95% CI, 1.103 to 2.161; P = 0.011), cerebrovascular disease (HR, 2.158; 95% CI, 1.309 to 3.557; P = 0.003), lower serum albumin (HR, 1.404; 95% CI, 1.001 to 1.968; P = 0.049), Charlson comorbidity index (CCI) scores with 4-5 (HR, 4.910; 95% CI, 2.327 to 10.357; P＜ 0.001), CCI scores with ≥6 (HR, 9.596; 95% CI, 4.807 to 19.158; P＜ 0.001) were the risk factors associated all-cause mortality of patients.Conclusions The elderly patients undergoing maintenance hemodialysis showed lower survival and higher mortality than young patients in China. Cardiovascular disease, cerebrovascular disease, serum albumin, CCI scores were the risk factors for all-cause mortality of young and elderly patients with maintenance hemodialysis.

Potassium titanyl phosphate (KTiOPO4, KTP) particle of nanometric size (nano-KTP) is an attractive material for nonlinear microscopy, and the optimized growth of large-size KTP single crystals has numerous applications for efficient frequency conversion in laser technology. Its three-dimensional orientation and nanoscale morphology are important for growth optimization. In this paper, we introduce an imaging technique based on circular dichroism second-harmonic generation (CD-SHG) to characterize the 3D distribution of KTP nanocrystal. A rigorous theoretical model of CD-SHG imaging for nano-KTP through stratified media is demonstrated. Circular dichroism analysis is used to probe the orientation of 3-axis with respect to the optical observation axis. The research results show that the azimuthal angle of the peak value (SHG) or valley value (CD-SHG) is strongly related to the excitation polarization when the KTP sample is excited by different circular polarizations. Importantly, the refractive index mismatches and the imaging depth also affect the azimuthal angle. Thus, the proposed framework enables a more precise quantitative analysis of the CD-SHG signal of KTP.

Previous studies have shown that sevoflurane has an inhibitory effect on tumor cells. So far, the effect of sevoflurane on hepatocellular carcinoma needs to be confirmed by more studies. HOX transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA (lncRNA), has been shown to enhance cancer cell proliferation and medication resistance. The inherent importance and biological function of HOTAIR in the course of lung cancer (LC) is, however, poorly unclear. HOTAIR was shown to be highly elevated in LC cells in this investigation. Impairment of function trials with sevoflurane indicated that it has anticancer effects on LC cell growth, apoptosis, and aerobic glycolysis. In a mechanistic manner, HOTAIR was related to HK2 mRNA and promoted expression and constancy. Additional research revealed that HOTAIR coupled with hexokinase 2 (HK2) mRNA and favorably controlled its stabilization in a traditional-component way. By HK2, the LC enhancement role was mediated. In summary, our data show that HOTAIR promotes the synthesis and proliferation of LC glycogen by increasing the transcription of HK2, and HOTAIR is likely to be a potential treatment for LC patients.