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Abstract Background Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. Methods In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut‐off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan–Meier method, and significant differences were evaluated by the log‐rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early‐stage disease (stage 0‐II) for sensitivity analysis. Results Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19‐9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p

Abstract Purpose Chemoradiotherapy (CRT) remains the standard treatment for locally advanced rectal cancer (LARC). This phase 2 clinical trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in LARC. Patients and methods The patients with LARC (the lower edge more than 5 cm from the anal verge) received up to 5 cycles of mFOLFOXIRI. MRI was performed to assess the baseline and postchemotherapy TN stage. Radical resection was performed within 4–6 weeks from the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2 and a positive CRM. The primary endpoint was the pathological complete response (pCR) rate. Results From February 2016 to March 2019, 50 patients were enrolled. Forty-eight (96%) were clinically node-positive, 28 (56.5%) with MRF invasion and 39 (78.4%) were EMVI positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range,1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients with cN + achieved a pathological node-negative status. The proportions of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively. Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or > toxicities included neutrocytopenia (50%), leukopenia (14%) and diarrhea (12%) during the neoadjuvant chemotherapy period. Clinically meaningful postoperative complications included pneumonia (n = 1), pelvic infection (n = 1) and anastomotic fistula (n = 1). With a median follow-up time of 51.2 months, local recurrences and distant metastases were confirmed in 3 (6.5%) and 9 (19.6%) of cases, respectively. The 3-year disease free survival (DFS) and overall survival (OS)rates were 75.8% and 86.8%. Conclusion Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect and seemed to be effective in eliminating EMVI and transforming the positive MRF to negative in LARC. The survival results are promising. The long-term follow-up showed promising DFS and OS rates accompanied by a favorable safety profile. Trial registration ClinicalTrials.gov identifier: NCT03443661, 23/02/2018.

Abstract Objective Real-world data (RWD) and real-world evidence (RWE) have been paid more and more attention in recent years. We aimed to evaluate the reporting quality of cohort studies using real-world data (RWD) published between 2013 and 2021 and analyze the possible factors. Methods We conducted a comprehensive search in Medline and Embase through the OVID interface for cohort studies published from 2013 to 2021 on April 29, 2022. Studies aimed at comparing the effectiveness or safety of exposure factors in the real-world setting were included. The evaluation was based on the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. Agreement for inclusion and evaluation was calculated using Cohen’s kappa. Pearson chi-square test or Fisher’s exact test and Mann-Whitney U test were used to analyze the possible factors, including the release of RECORD, journal IFs, and article citations. Bonferroni’s correction was conducted for multiple comparisons. Interrupted time series analysis was performed to display the changes in report quality over time. Results 187 articles were finally included. The mean ± SD of the percentage of adequately reported items in the 187 articles was 44.7 ± 14.3 with a range of 11.1–87%. Of 23 items, the adequate reporting rate of 10 items reached 50%, and the reporting rate of some vital items was inadequate. After Bonferroni’s correction, the reporting of only one item significantly improved after the release of RECORD and there was no significant improvement in the overall report quality. For interrupted time series analysis, there were no significant changes in the slope (p = 0.42) and level (p = 0.12) of adequate reporting rate. The journal IFs and citations were respectively related to 2 areas and the former significantly higher in high-reporting quality articles. Conclusion The endorsement of the RECORD cheklist was generally inadequate in cohort studies using RWD and has not improved in recent years. We encourage researchers to endorse relevant guidelines when utilizing RWD for research.

Abstract Viral tracers that enable efficient retrograde labeling of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Currently, some recombinant adeno-associated viruses (rAAVs) based on capsid engineering are widely used for retrograde tracing, but display undesirable brain area selectivity due to inefficient retrograde transduction in certain neural connections. Here we developed an easily editable toolkit to produce high titer AAV11 and demonstrated that it exhibits potent and stringent retrograde labeling of projection neurons in adult male wild-type or Cre transgenic mice. AAV11 can function as a powerful retrograde viral tracer complementary to AAV2-retro in multiple neural connections. In combination with fiber photometry, AAV11 can be used to monitor neuronal activities in the functional network by retrograde delivering calcium-sensitive indicator under the control of a neuron-specific promoter or the Cre-lox system. Furthermore, we showed that GfaABC1D promoter embedding AAV11 is superior to AAV8 and AAV5 in astrocytic tropism in vivo, combined with bidirectional multi-vector axoastrocytic labeling, AAV11 can be used to study neuron-astrocyte connection. Finally, we showed that AAV11 allows for analyzing circuit connectivity difference in the brains of the Alzheimer’s disease and control mice. These properties make AAV11 a promising tool for mapping and manipulating neural circuits and for gene therapy of some neurological and neurodegenerative disorders.

Abstract Background Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. Methods This was a multi‐center, single‐arm study that enrolled MIBC patients with a clinical stage of T2‐4aN0‐1M0, and scheduled for RC. Patients received three 21‐day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). Results From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune‐related AEs were all grade 1 or 2. Pathologic response was not correlated with PD‐L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. Conclusions Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti‐tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.

Abstract Introduction Farmlands are key sources of greenhouse gas (GHG) emissions, which are susceptible to changes in precipitation regimes. The soils of seasonal fallow contribute approximately half of annual GHG emissions from farmlands, but the effect of precipitation frequency on soil GHG emissions from seasonal fallow croplands remains virtually unknown. Materials and Methods We conducted a microcosm study to evaluate the response of nitrous oxide (N2O), methane (CH4) and carbon dioxide (CO2) fluxes from typical paddy and upland soils to the changes in watering frequency simulating precipitation scenarios of subtropical regions during seasonal fallow. We also analyzed changes of soil properties and biotic characteristics associated with GHG emissions, including abundances of soil denitrifiers (nirK, nirS, nosZI and nosZII genes), methanotrophs (pmoA gene) and methanogens (mcrA gene) to altered watering frequency. Results Increased watering frequency led to overall increases in soil N2O and CO2 fluxes compared with low frequency. Compared with low frequency, high watering frequency decreased CH4 flux from the paddy soil by 3.5 times, while enhanced CH4 flux from the upland soil by 60%. Furthermore, the increased watering frequency had positive effects on cumulative N2O and CO2 fluxes from the upland soil, whereas no similar trend was observed for the paddy soil. Hierarchical partitioning analyses showed that N2O fluxes from the paddy soil were mostly related to nitrogen availability, and mcrA gene abundance had more than 90% of relative independent effects on CH4 and CO2 fluxes from the paddy soil. For the upland soil, nosZ (60.34%), pmoA (53.18%) and nir (47.07%) gene abundances were important predictors of N2O, CH4 and CO2 fluxes, respectively. Conclusion Our results demonstrate that increased watering frequency facilitates GHG emissions by changing soil properties and functional gene abundances. These findings provide new insights into GHG fluxes from seasonal fallow croplands in response to altered precipitation patterns.

Objective To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI).Methods A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters.Results IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91).Conclusion The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

Background: Currently, there is no recommended standard third-line chemotherapy for metastatic gastric cancer. Objectives: In this study, we aimed to evaluate irinotecan’s efficacy and safety in treating metastatic gastric cancer after the failure of first- and second-line chemotherapy. Design: Prospective single-arm, two-center, phase II trial. Methods: Patients were aged 18–70 years, with histologically confirmed gastric adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0–1, progressed during or within 3 months following the last administration of second-line chemotherapy and had no other severe hematologic, cardiac, pulmonary, hepatic, or renal functional abnormalities or immunodeficiency diseases. Eligible patients received 28-day cycles of irinotecan (180 mg/m 2 intravenously, days 1 and 15) and were assessed according to the RECIST 1.1 criteria every two cycles. Patients who discontinued treatment for any reason were followed up every 2 months until death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results: A total of 98 eligible patients were enrolled in this study. In the intention-to-treat population, the median OS was 7.17 months, the median PFS was 3.47 months, and the ORR and DCR were 4.08% and 47.96%, respectively. In the per-protocol population, the median OS was 7.77 months, the median PFS was 3.47 months, and the ORR and DCR were 4.82% and 50.60%, respectively. The incidence of grade 3 or 4 hematological and non-hematological toxicities was 19.4%, and none of the patients died owing to adverse events. Cox regression analysis revealed neutropenia and baseline thrombocyte levels were independently correlated with PFS and OS. Conclusion: Irinotecan monotherapy is an efficient, well-tolerated, and economical third-line treatment for patients with metastatic gastric cancer as a third-line treatment. Trial registration: ClinicalTrials.gov identifier: NCT02662959.

The incidence of reporting caliciviruses in wild birds is less common than in other animals, and the majority of cases remain unclassified. A strain of calicivirus was discovered in this study in the feces of cormorants collected at Xiamen Horticulture Expo Garden in 2021 and was named Cormcali01. The genome of Cormcali01 was 8,561 bp in length which contained characteristic motifs present in other caliciviruses. Furthermore, it demonstrated a significant deviation from all existing calicivirus nucleotide sequences, exhibiting the highest amino acid identity (47.34%) to the unclassified Ruddy turnstone calicivirus A. A pairwise comparison of the VP1 protein showed that Cormcali01 had the highest amino acid identity of 43.90% with the unassigned Ruddy turnstone calicivirus A. Phylogenetic analysis demonstrated that VP1 of Cormcali01 clustered with unassigned caliciviruses. Therefore, based on phylogenetic analysis and pairwise comparison, Cormcali01 should be affiliated with the unassigned calicivirus, which were suggested to comprise a new calicivirus genus, the Sanovirus genus. After investigating the prevalence of Cormcali01, we discovered that 22.22% of fecal samples (10/45) were tested positive. These findings expand our understanding of the genetic variation of caliciviruses and provide valuable epidemiological information regarding a potential outbreak of calicivirus disease in birds.

The imbalance of the lateral shoulder is reflected by the clavicle angle (CA) in radiology. It remains unclear how to achieve postoperative lateral shoulder balance (LSB) after spinal deformity correction surgery. A retrospective analysis was conducted on AIS patients who underwent surgery by the same spine surgeon at our hospital from 2016 to 2020. A total of 110 patients with spinal deformity were included in the study to verify the correlation between the T1–T5 tilt angle and CA before and after surgery, as well as the relation-ship between the change in T1–T5 tilt angle before and after surgery and the change in CA before and after surgery. By comparing the correlation coefficients, it was found that there may not be a direct relationship between the pre- and postoperative tilt angles of T1–5 and CA, but their changes were closely related to the changes in CA. The change in T1 tilt angle after orthopaedic surgery was significantly correlated with the change in CA, with a correlation coefficient of 0.976, indicating a close relationship between T1 and the clavicle. As the vertebrae moved down, the correlation gradually decreased. In summary, this study suggests that there is a close relationship between T1–T5 and the clavicle and that the change in T1 tilt angle after spinal scoliosis correction surgery is significantly correlated with CA, which decreases as the vertebra moves down.

Jiajin Mountain, where the giant pandas reside, is an essential nature reserve in China. To comprehend the land use classification of the habitat, this article proposes a remote sensing interpretation algorithm based on spatial case reasoning, known as spatial case-based reasoning (SCBR). The algorithm incorporates specific spatial factors into its framework and does not require an extensive amount of domain knowledge and eliminates the need for a complex model training process, making it capable of completing land use classification in the study area. SCBR comprises a spatial case expression model and a spatial case similarity reasoning model. The paper conducted comparative experiments between the proposed algorithm and support vector machine (SVM), U-Net, vision transformer (ViT), and Trans-Unet, and the results demonstrate that spatial case-based reasoning produces superior classification outcomes. The land use classification experiment based on spatial case-based reasoning at the Jiajinshan giant panda habitat produced satisfactory experimental results. In the comparative experiments, the overall accuracy of SCBR classification reached 95%, and the Kappa coefficient reached 90%. The paper further analyzed the changes in land use classification from 2018 to 2022, and the average accuracy consistently exceeds 80%. We discovered that the ecological environment in the region where the giant pandas reside has experienced significant improvement, particularly in forest protection and restoration. This study provides a theoretical basis for the ecological environment protection of the area.

Pigs are natural host to various zoonotic pathogens including viruses. In this study, we analyzed the viral communities in the feces of 89 piglets with diarrhea under one month old which were collected from six farms in Jiangsu Province of the Eastern China, using the unbiased virus metagenomic method. A total of 89 libraries were constructed, and 46937894 unique sequence reads were generated by Illumina sequencing. Overall, the family Picornaviridae accounted for the majority of the total reads of putative mammalian viruses. Ten novel virus genomes from different family members were discovered, including Parvoviridae (n = 2), Picobirnaviridae (n = 4) and CRESS DNA viruses (n = 4). A large number of phages were identified, which mainly belonged to the order Caudovirales and the family Microviridae. Moreover, some identified viruses were closely related to viruses found in non-porcine hosts, highlighting the potential for cross-species virus dissemination. This study increased our understanding of the fecal virus communities of diarrhea piglets and provided valuable information for virus monitoring and preventing.

Bio-based materials have garnered considerable attention in the flame retardant field due to their inherent safety and environmental benefits. This study introduces a novel and eco-friendly flame retardant prepared through the Maillard reaction between glucose and poly(glutamic acid) for treating silk fabric. The study elucidates the synthesis of Maillard reaction products (MRPs) and verifies their deposition onto the silk fabric surface by observing changes in surface morphology, functional groups, and charged characteristics. The flammability tests demonstrate that MRPs treated silk fabrics had a high limiting oxygen index of over 27 % and a charred length of less than 12 cm, indicating effective flame retardancy. Moreover, the introduction of MRPs led to a significant decrease in smoke release when silk fabric underwent combustion. This observation can be attributed to the enhanced char formation and increased thermal degradation temperature of MRPs treated silk fabric. The electrostatic interaction between silk fiber and MRPs contributed to the fabric's resistance to repeated washing. Moreover, MRPs treated silk fabric retained their tensile properties and showed enhanced wrinkle-resistant performance. Generally, this research opens up a new path for the green preparation of halogen-free and phosphorus-free flame retardant protein fibers.

Summary: Background: Limited therapeutic options are available for metastatic colorectal cancer (mCRC) patients after failure of first- and second-line therapies, representing an unmet medical need for novel therapies. Methods: This is an open-label, single arm, multicenter, phase Ⅱ study aiming to perform the efficacy, safety and genomic analysis of SCT200, a noval fully humanized IgG1 anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type mCRC. SCT200 (6 mg/kg) was given weekly for the first six weeks, followed by a higher dose of 8 mg/kg every two weeks until disease progression or unacceptable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) and secondary endpoints included ORR in patients with left-sided tumor, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Findings: From February 12, 2018 to December 1, 2019, a total of 110 patients aged between 26 and 77 years (median: 55; interquartile range [IQR]: 47–63) with fluorouracil, oxaliplatin, and irinotecan refractory RAS and BRAF wild-type mCRC were enrolled from 22 hospitals in China. As the data cut-off date on May 15, 2020, the IRC-assessed ORR and DCR was 31% (34/110, 95% confidence interval [CI] 22–40%) and 75% (82/110, 95% CI 65–82%), respectively. Thirty one percent (34/110) patients achieved confirmed partial response (PR). The median PFS and median OS were 5.1 months (95% CI 3.4–5.2) and 16.2 months (95% CI 11.1-not available [NA]), respectively. The most common ≥ grade 3 treatment-related adverse events (TRAEs) were hypomagnesemia (17%, 19/110) and acneiform dermatitis (11%, 12/110). No deaths occurred. Genomic analysis suggested positive association between MYC amplification and patients’ response (P = 0.0058). RAS/RAF mutation and MET amplification were the most frequently detected resistance mechanisms. Patients with high circulating tumor DNA (ctDNA) at baseline or without ctDNA clearance at the 7th week after the first dose of SCT200 administration before receiving SCT200 had worse PFS and OS. Interpretation: SCT200 exhibited promising clinical efficacy and manageable safety profiles in RAS and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for RAS and BRAF wild-type mCRC patients with SCT200 therapy. Funding: This study was sponsored by Sinocelltech Ltd., Beijing, China and partly supported by the National Science and Technology Major Project for Key New Drug Development (2019ZX09732001-006, 2017ZX09304015).

Currently, there is an absence of an exhaustive elucidation regarding the long-term spatiotemporal characteristics of meteorological droughts in China. Previous studies have predominantly fixated on the lower-dimensional (temporal or spatial) facets of drought events, overlooking critical spatiotemporal details. This paper proposes an integrated processing framework that employs a three-dimensional clustering algorithm to discern drought events and quantifies the spatiotemporal patterns and dynamic attributes of China’s meteorological droughts during 1950–2021 from a three-dimensional perspective encompassing longitude, latitude, and time, capturing comprehensive spatiotemporal information. Additionally, the cross wavelet transform is harnessed to elucidate the impact of teleconnection factors on meteorological drought. The findings underscore that prolonged and extensive meteorological drought events, characterized by heightened severity, primarily manifest during the 1950 s, 1960 s, and 2010 s in temporal, predominantly within the central and western China spatially. From 1950 onwards, the severity, duration, and affected area of meteorological droughts in China exhibit a discernible pattern of initial decline followed by escalation. Into the 2010 s, meteorological droughts became more severe and active. China's meteorological drought displays two relatively prevailing spatial migration patterns: an overarching eastward and westward migration. In the former, the most frequent migration occurs to the east and northeast during its monthly evolution, while the latter involves migration primarily towards the west, southwest, and northwest. The impact of teleconnection factors on meteorological drought shows a spatiotemporal heterogeneity, with ENSO exhibiting a relatively substantial and intricate influencer. This research unearths the latest long-term spatiotemporal dynamics of meteorological drought in China, which contributes to an improved comprehension of drought patterns and behaviors.

Mesenchymal stem cells (MSCs) are highly effective in the treatment of acute liver failure (ALF). The efficacy of MSCs is closely related to the inflammatory environment. Therefore, we investigated the functional changes of MSCs in response to interleukin-33 (IL-33) stimulation. The results showed that bone marrow mesenchymal stem cells (BMSCs) pretreated with IL-33 had increased CCR2 expression, targeted CCL2 in the injured liver tissue, and improved the migration ability. Under LPS stimulation, the NF-κB pathway of BMDM was activated, and its phenotype polarized to the M1-type, while BMSCs pretreated with IL-33 inhibited the NF-κB pathway and enhanced M2 macrophage polarization. The M2-type macrophages could further inhibit hepatocytes inflammation, reduce hepatocytes apoptosis, and promote hepatocytes repair. These results suggest that IL-33 can enhance the efficacy of BMSCs in ALF and provide a new strategy for cell therapy of liver diseases.

In traffic engineering design in saline soil environments, a salt barrier is usually installed in the embankment to prevent secondary salinization damage on the upper embankment and road surface. However, using this salt barrier method in saline soil subgrade projects in cold and arid highland areas has led to the problem of salt barrier failure, and the failure mechanism remains unclear. The study was performed in the saline soil distribution area in the Qaidam Basin on the northeastern part of the Qinghai–Tibet Plateau. We collected samples from the natural saline soil foundation and the structural layer of the subgrade soil using the method of excavating a road section that had undergone salt barrier failure. Laboratory tests and theoretical calculations were carried out on the particle gradation of the natural saline soils and the structural subgrade soil layers. In addition, their water and salt transport heights and the failure mechanism of the subgrade salt barrier were studied. The results showed that salt chemistry increases the capillary force between the soil grains in highly saline soil environments. This increases the water–salt transport of more than 850.00 mm in saline soils, which is much greater than the capillary water rise in ordinary soils (463.0–650.0 mm). When no water barrier geotextile layer is set in the subgrade structure, there is frequently a high headwater and salt transport in the soil layer of the subgrade structure for a long time. There is continuous vapor and salt transport in the large pores of the coarse-grained salt barrier. The vibration load of the road surface causes the fine soil particles to migrate downward into the coarse-grained salt barrier, reducing the thickness of the salt barrier. Under the combined effect of these three effects, the salt barrier of the saline soil subgrade in cold and arid areas fails to resist salt migration, and the subgrade is prone to secondary salinization.

The aim of this systematic review was to describe the efficacy and acceptability of natural products in the management of oral mucositis caused by radiation. From the day it started to August 7, 2023, a thorough search for randomized controlled trials (RCTs) was carried out among seven databases: the Web of Science, PubMed, Embase, OVID, Scopus, the Cochrane Library and the CINAHL database. Only English-language articles were identified during the search. Using the revised Cochrane risk-of-bias tool, version 2, two researchers screened the articles, collected information on study characteristics, and appraised risks of bias. The data were analyzed and descriptively presented with a narrative synthesis methodology involving the Synthesis Without Meta-Analysis (SWiM) reporting element applied in detail. The PROSPERO registration number of this study is CRD42023476932. Thirty-six clinical trials were included in the study; the included studies included a variety of 20 types of natural products. Honey and Curcuma longa were the most commonly assessed natural products. A total of 2,400 participants reported taking part in therapy with natural products for oral mucositis. Natural products demonstrated substantial efficacy in terms of influencing intensity, incidence, pain score, quality of life, and symptoms such as xerostomia and dysphagia. Except for manuka honey, most natural products were well accepted. Regarding the clinical trials' risk of bias, 2 clinical trials (5.56%) had a high risk of bias, 17 studies (47.2%) had a low risk of bias, and 17 studies (47.2%) were rated with "some concern." Natural remedies work well as alternate treatments for managing oral mucositis caused by radiation therapy. However, additional clinical trials are still needed. The safety of these conventional medications as well as their effectiveness and safety when used in combination with other conventional or naturopathic therapies should be fully examined.

Two questions in the research of animal personality—whether there is a correlation between a personality trait and individual reproductive success, and what is the genetic basis underlying a personality trait—remain unresolved. We addressed these two questions in three shrub-nesting birds, the Azure-winged Magpie (Cyanopica cyanus, AM), White-collared Blackbird (Turdus albocinctus, WB), and Brown-cheeked Laughingthrush (Trochalopteron henrici, BL). The personality type of an individual was first identified according to its response to a territorial intruder. Then, we compared the fleeing distance, breeding parameters, and differential expressed genes (DEGs) in the brain transcriptome between bold and shy breeders. In the three species, bold breeders exhibited more aggressiveness towards an intruder of their territory than did shy breeders. The reproductive success of bold breeders was significantly higher than that of shy breeders in AM but not in WB and BL. The three species shared one DEG, crabp1, which was up-regulated in bold relative to in shy individuals. By regulating the expression of corticotropin-releasing hormone, higher crabp1 gene expression can decrease cellular response to retinoic acid. Therefore, bold individuals are insensitive to external stresses and able to exhibit more aggressiveness to intruders than their shier counterparts. Aggressiveness is beneficial to bold individuals in AM but not in WB and BL because the former could evoke neighbors to make the same response of defending against intruders but the latter could not. Although a personality trait may have the same genetic basis across species, its correlation with reproductive success depends largely on the life history style of a species.

Objective: Polypharmacy prevalence is increasing worldwide, and it is becoming more popular among the elderly. This study aimed to compare the prevalence of potentially inappropriate medications (PIMs) using the Beers criteria (2019 edition), criteria for potentially inappropriate medications for older adults in China (Chinese criteria), Screening Tool of Older Persons’ Prescriptions (STOPP), and Screening Tool to Alert to Right Treatment (START) criteria and to identify risk factors associated with PIM use.Methods: This was a cross-sectional study with a sample of 276 inpatients aged ≥65 years old from January 2020 to June 2020. A cross-sectional study was conducted to analyze PIMs based on the Beers (2019 edition), Chinese, STOPP, and START criteria. PIMs use was analysed based on four different criteria and logistic regression analysis was used to investigate independent factors associated with PIM use.Results: The mean number of medications used by the elderly population was nine (range, 0–28). A total of 252 patients (accounting for 91.30%) took five or more medications and 120 patients (accounting for 43.48%) took 10 or more medications. The prevalence rates of PIMs were 66.30% (183/276), 55.07% (152/276), 26.45% (73/276), and 64.13% (177/276) determined by the Beers, Chinese, STOPP, and START criteria, respectively. The top PIMs screened using the Beers, Chinese, and STOPP criteria were proton pump inhibitors, clopidogrel, and benzodiazepines, respectively. Missed use of ACEI in patients with systolic heart failure and/or coronary artery disease was found to be the most common potential prescription omission (PPOs) analyzed using the START criteria. Logistic regression analysis showed that the strongest predictor of PIMs, as determined by all four criteria, was an increased number of medications (p < 0.001). Age was another risk factor for PIMs based on the STOPP criteria in our study (p < 0.05).Conclusion: Polypharmacy and PIMs were common in our study, and the risk of PIMs correlated with polypharmacy. Application of the Beers, Chinese, STOPP, and START criteria is a useful tool for detecting PIM use.

Microplastics (MPs) pollution is becoming an emerging global stressor for soil ecosystems. However, studies on the impacts of biodegradable MPs on soil C sequestration have been mainly based on bulk C quantity, without considering the storage form of C, its persistency and N demand. To address this issue, the common poly (butylene adipate-co-terephthalate) (PBAT) was used as the model, and its effects on soil functional organic pools, including mineral-associated (MAOM), particulate (POM) and dissolved organic matter (DOM), were investigated from the novel coupled perspective of C and N stocks. After adding PBAT-MPs, the contents of soil POM-C, DOM-C, and MAOM-C were increased by 546.9 %–697.8 %, 54.2 %–90.3 %, and 13.7 %–18.9 %, respectively. Accordingly, the total C increased by 116.0 %–191.1 %. Structural equation modeling showed that soil C pools were regulated by PBAT input and microbial metabolism associated with C and N enzymes. Specifically, PBAT debris could be disguised as soil C to promote POM formation, which was the main pathway for C accumulation. Inversely, the MAOM-C and DOM-C formation was attributed to the PBAT microbial product and the selective consumption in DOM-N. Random forest model confirmed that N-activated (e.g., Nitrospirae) and PBAT-degrading bacteria (e.g., Gemmatinadetes) were important taxa for soil C accumulation, and the key enzymes were rhizopus oryzae lipas, invertase, and ammonia monooxygenase. The soil N accumulation was mainly related to the oligotrophic taxa (e.g., Chloroflexi and Ascomycota) associated with aggregate formation, decreasing the DOM-N by 46.9 %–84.3 %, but did not significantly change the total N storage and other N pools. Collectively, the findings highlight the urgency to control the nutrient imbalance risk of labile N loss and recalcitrant C enrichment in POM to avoid the depressed turnover rate of organic matter in MPs-polluted soil.

Importance: The global COVID-19 pandemic does not appear to end in the near future. Currently, limited data are available on the risk factors for delayed viral clearance in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Objective: This study aimed to investigate the association of clinical characteristics and vaccination with prolonged viral clearance. Methods: This retrospective cohort included 16,985 patients who had contracted the SARS-CoV-2 Omicron variant between April 5 and May 30, 2022, in Shanghai, China, and had mild or no symptoms. The patients were admitted to the quarantine venue at the Shanghai New International Expo Center. Results: Of the 16,985 participants, the occurrence of viral clearance was ≤8 and > 8 days in 11,009 (64.8 %) and 5976 (35.2 %) participants, respectively. Risk factors related to patients who remained persistently polymerase chain reaction (PCR)-positive were sex (Male, odds ratio [OR] 1.221, p 35, OR 0.079, p

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The efficacy of the top hit, Erlotinib, extended to human cells, where it blocked Wnt/β-catenin signaling downstream of the destruction complex. Notably, Erlotinib treatment reduced self-renewal in human T-cell Acute Lymphoblastic Leukemia cells, which rely on active β-catenin signaling for maintenance of leukemia-initiating cells. Erlotinib also reduced leukemia-initiating cell frequency and delayed disease formation in zebrafish models. This study underscores zebrafish’s translational potential in drug discovery and repurposing and highlights a new use for Erlotinib as a Wnt inhibitor for cancers driven by aberrant Wnt/β-catenin signaling.

Zingiber mioga is a highly economic crop that is used to produce vegetables, spices and herbal pharmaceuticals. Its edible flower bud contributes most to the economic value, but the big leaves were discarded as agricultural waste, which urgently needs to be exploited. In this work, polysaccharides from waste Z. mioga leaves (PWZMLs) were extracted using ultrasonic-microwave-assisted extraction (UMAE). After purification and characterization, the antioxidation and anticoagulation of PWZMLs were evaluated to appraise the potential in cardiovascular protection. Under the liquid–solid ratio of 26: 1 mL/g, after ultrasonication at 495 W for 10 min, followed by microwaving at 490 W for 5 min, the yield of PWZMLs achieved to 6.22 ± 0.14 %, notably higher (P

Abstract Lanthanide (Ln3+) oxysulfide nanocrystals (NCs) have great prospect in many advanced technologies; however, they suffer from a low photoluminescence efficiency due to the volatility of sulfur and deleterious surface quenching effect. Herein, we report a novel sandwiched luminescent heterostructure based on Ln3+‐doped Gd2O2S@NaYF4 core/shell NCs with tunable sulfur content in the sandwich layer. By means of Eu3+ as the sensitive structural probes, we unravel the ligand‐mediated structure control of the NCs from Gd2O3: Ln3+@NaYF4 to Gd2O2S: Ln3+@NaYF4 with tailored S2– deficiency. Such a sandwich‐type core/shell heterostructure enables us to achieve efficient and multicolor downshifting and upconversion luminescence (UCL), with up to 208.8 folds of enhancement in UCL intensity as compared to that of their core‐only counterparts. These findings provide a general approach for the controlled synthesis of lanthanide oxysulfide@fluoride heterostructure, which offers a new way for the materials design towards diverse emerging applications.

Abstract Microneedles (MNs) have been broadly used for transdermal delivery of a variety of drugs, ranging from small chemicals to biological macromolecules, due to the properties of increased drug permeability, minimal invasiveness and improved patient compliance. Despite these MNs can be made of different materials, such as metal, silicon, and glass, polymers have attracted the most attention as a microneedle (MN) matrix because of their excellent biocompatibility and biodegradability, which eliminates the requirement of MN removal after drug release. To satisfy different needs of transdermal drug delivery, polymeric MNs have been fabricated with several special designs. In this review, we summarize the advancement of the fabrication designs of polymeric MNs, including integrated MNs, two‐segment MNs, core‐shell or multi‐layered MNs, and arrowhead MNs. The related biomedical applications of MNs with these different specific designs are also discussed. Finally, we provide our perspectives on the future development of polymeric MNs.

Objective: The treatment for posterolateral tibial plateau fractures (PTPF) have been subjects of controversy. We conducted a study to improve the fixation of PTPF through a lateral approach.Methods: We utilized 40 synthetic tibias and categorized the fracture models into five groups based on the locking compression plate (LCP) and T-distal radius plate (TPP) via various forms of fixation with screws through the posterolateral (PL) fracture fragments. I: Two-screw fixation using two locking screws (LPTL). Ⅱ: Two-screw fixation with both variable angle locking screws (LPTV). Ⅲ: One-screw fixation with one locking screw (LPOL). Ⅳ: One-screw fixation with one locking screw and two anteroposterior lag screws (LPOLTL). Ⅴ: a distal radius plate with three locking screws (TPP). Biomechanical tests were conducted to observe the axial compression displacement of the PL fracture fragments at force levels of 250 N, 500 N, and 750 N, as well as to determine the failure load and the axial stiffness for each respective group.Results: Under a 750 N load condition, the displacements within the five experimental groups exhibited the following trend: Ⅴ < Ⅱ < Ⅰ< Ⅳ < Ⅲ. However, there were no significant differences between Group V and Group II, Group I and Group IV (p > 0.05), and only Group Ⅲ demonstrated a displacement exceeding 3 mm. The failure load and the axial stiffness exhibited the same trend. Conversely, statistical significance was identified among the remaining group compared with Group Ⅲ (p < 0.05). Regarding the finite element analysis, the maximum displacements for the five models under the load of 750 N exhibited the following trend: Ⅴ < Ⅱ < Ⅰ< Ⅳ < Ⅲ. The following trends were observed in maximum von Mises stresses for these models under the load of 750 N: Ⅴ < Ⅱ < Ⅳ< Ⅰ < Ⅲ.Conclusion: It is crucial to address the inadequate mechanical strength associated with single screw fixation of LCP for fixing PL fractures in a clinical setting. The biomechanical strength of two-screw fixation surpasses that of single-screw fixation. Introducing variable-angle screws can further enhance the fixation range. Furthermore, the addition of two lag screws threaded from anterior to posterior can compensate the mechanical stability, when PL fracture is fixed with single screw in clinic.

AbstractObjective This study aimed to evaluate the effectiveness of double ABCX-based psychotherapy for psychological distress during in vitro fertilization-embryo transfer (IVF-ET) among a female group (FG), couple group (CoG) and control group (CG).Methods A total of 201 women undergoing their first IVF-ET cycle were randomized into three groups. The 6-session intervention was delivered at each visit to the IVF clinic. The primary outcomes were depression and anxiety, and the secondary outcomes included sleep quality, serum cortisol (nmol/L) levels and the clinical pregnancy rate, which were assessed before and after the intervention.Results The group-by-time effects were significant for depression, anxiety, sleep quality and serum cortisol levels, with larger effect sizes in the FG than in the CoG. There was no significant difference in the pregnancy rate among the three groups.Conclusion Psychotherapy effectively mitigated psychological distress, suggesting greater effectiveness for couples undergoing IVF couples than for women only. It is structured and easy to use during the IVF treatment cycle.Trial registration number https://register.clinicaltrials.gov (NCT03931187, retrospectively registered on April 23, 2019)

Urban land use/land cover (LULC) classification has long been a hotspot for remote sensing applications. With high spatio-temporal resolution and multispectral, the recently launched GF-6 satellite provides ideal open imagery for LULC mapping. In this study, we utilized multitemporal GF-6 images to generate six types of land features, including spectral bands, texture features, built-up, waterbody, vegetation, and red-edge indices. The minimum Redundancy Maximum Relevance (mRMR) algorithm was employed to optimize feature selection. Subsequently, Random Forest (RF) and Extreme Gradient Boosting (XGBT) were assessed using different feature selections. Besides, various feature configurations were designed for LULC classification and comparison. The results indicate that the mRMR-based RF method achieved the highest overall accuracy of 91.37%. The temporal red-edge indices were important features for urban LULC classification and contributed mainly to grassland and cropland. These results supplement existing classification methods and assist in improving LULC mapping in urban areas with complex landscapes.

Landslides in high-order position areas pose a serious threat to residents located below such areas. Therefore, research on the evolution process and underlying dynamic mechanisms is crucial. The majority of relevant studies are based on landslides that have already occurred; however, the investigation of potential landslides is of higher value. In this study, a progressive potential landslide identification method is proposed with the application of SBAS-InSAR (Small Baseline Subset Interferometric Synthetic Aperture Radar) and subsequently combined with Google Earth, GF-1 (Gaofen-1), GF-2 (Gaofen-2), ZY-3 (Ziyuan-3) and UAV (Unmanned Aerial Vehicle) imagery, and DEM (Digital Elevation Model) for further validation. The proposed method is employed to determine the potential landslide in Tuanjiecun by integrating the multi-period data to simultaneously analyze the evolution and mechanism of the potential landslide. The long short-term memory method is then adopted to predict the evolution trend based on accumulative deformation from SBAS-InSAR. The results suggest that the deformation of Tuanjiecun potential landslide will increase to −238.57 mm. This article provides a new approach for disaster prevention and mitigation by determining a potential landslide using composite remote sensing and predicting the development of the potential landslide on indirect contact monitoring.

Objective This study analyzed the long-term arteriovenous fistula (AVF) patency rate and its determinants in patients undergoing maintenance hemodialysis.Methods General data and laboratory examinations of hemodialysis patients were collected retrospectively. The primary patency time, primary functional patency time, cumulative patency time, cumulative functional patency time, and temporary central venous catheterization (CVC) time were counted. Cox regression was used to analyze the relationships between different factors and AVF survival time. Kaplan-Meier survival analysis was used to analyze the primary patency, primary functional patency, cumulative patency, and cumulative functional patency rates between different groups.Results A total of 174 patients were included (mean age 58.38 ± 15.35 years), 57 women (32.76%) and 68 diabetics (39.08%). Univariate and multivariate Cox regression showed a correlation between UCR and AVF primary patency time, primary functional patency time, cumulative patency time, and cumulative functional patency time (HR 1.127, 1.116, 1.127, 1.115, 1.088, 1.075, 1.087, 1.013; 95%CI 1.055–1.204, 1.043–1.194, 1.055–1.204, 1.042–1.194, 1.022–1.158, 1.006–1.149, 1.021–1.157, 1.004–1.147; p 10.11 group are lower than those with UCR ≤ 10.11 (χ2 = 10.745, 10.712, 4.605, 4.472; p = 0.001, 0.001, 0.032, 0.034, respectively). The group of DTCP ≤ 42 days is better than DTCP > 42 days (χ2 = 6.014, 6.055, 8.572, 8.461; p = 0.014, 0.014, 0.003, 0.004, respectively).Conclusion Women with high UCR values at the beginning of dialysis and a long duration of temporary CVC have a poor long-term survival rate of AVF. Therefore, UCR can be used as an indicator to predict the long-term survival rate of AVF. Simultaneously, clinicians should remove the temporary catheter as early as possible if conditions permit it.

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j–4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50 = 2.68 ± 0.27 μM). In further studies, 12j–4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3β, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j–4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.

ABSTRACTDiarrhea is a leading cause of morbidity and mortality in children worldwide and represents a major dysbiosis event. Rotavirus has been recognized as a global leading pathogen of diarrhea. This study is aimed at investigating differences in the gut virome between diarrheal children and healthy controls. In 2018, 76 diarrheal fecal samples and 27 healthy fecal samples in Shanghai and 40 diarrheal fecal samples and 19 healthy fecal samples in Taizhou were collected to investigate the composition of the gut virome. Viral metagenomic analyses revealed that the alpha diversity of the diarrheal virome was not significantly different from that of the healthy virome, and the beta diversity had a significant difference between diarrheal and healthy children. The diarrheal virome was mainly dominated by the families Adenoviridae, Astroviridae, Caliciviridae, and Picornaviridae. Meanwhile, the healthy virome also contains phages, including Microviridae and Caudovirales. The high prevalence of diverse enteric viruses in all samples and the little abundance of Microviridae and Caudovirales in diarrheal groups were identified. The study introduced a general overview of the gut virome in diarrheal children, revealed the compositional differences in the gut viral community compared to healthy controls, and provided a reference for efficient treatments and prevention of virus-infectious diarrhea in children.

AbstractObjective To evaluate the feasibility of using an intrarectal Foley catheter during ultrasound-guided high-intensity focused ultrasound (US-HIFU) in patients with benign uterine diseases of the posterior wall beyond the HIFU therapeutic range.Methods Patients were treated with US-HIFU and lesion changes were monitored using contrast-enhanced MRI from June 2020 to September 2021. A Foley catheter was inserted into the rectum to facilitate a successful US-HIFU ablation. Complications and lesion responses were recorded during the treatment and follow-up.Results Thirteen patients with 14 lesions beyond the device’s treatable area were enrolled. The average placement time and insertion depth of the intrarectal Foley catheter was 7.6 ± 2.7 min and 23.2 ± 7.6 cm, respectively. A median of 50 mL degassed water was injected into the Foley catheter balloon. All 14 lesions were successfully pushed into a treatable area and subjected to HIFU. The average treatment time, irradiation time, and total therapeutic energy of HIFU were 44.2 ± 17.3 min, 394.4 ± 295.7 s, and 73.3 ± 46.6 kJ, respectively. The mean non-perfusion volume (NPV) in all treated lesions was 23.2 ± 19.2 cm3, and the mean NPV ratio was 57.8 ± 16.9%. Major complications were not observed.Conclusion Intrarectal Foley catheter-assisted US-HIFU is effective and safe. Its clinical application could benefit patients with benign uterine diseases outside the HIFU therapeutic range.

AbstractDoxorubicin (DOX) is a commonly studied chemotherapeutic agent for the treatment of solid tumors, but the severe side effects limit its clinical application. It is shown that DOX-metal chelate has lower in vitro cytotoxicity compared with DOX, as the anthracyclines of DOX can form coordinative interaction with transition metal ions. In addition, the transition metal ions could catalyze the production of hydroxyl radicals (·OH) via Fenton/Fenton-like reactions to achieve antitumor chemodynamic therapy (CDT). In this study, copper ions (Cu2+) were applied to obtain DOX/Cu(II) prodrug, and a liposomal formulation was used to avoid the rapid blood clearance and optimize the biodistribution of this prodrug. In vitro and in vivo antitumor results demonstrated that this pH sensitive Cu-chelating prodrug can reduce adverse effects of DOX but improve the antitumor efficiency due to the combination of chemotherapy and chemodynamic therapy. Our study provided a facile and effective approach of metal-chelating prodrug strategy for combination cancer therapy strategy.

Abstract Purpose Distant metastasis (DM) and neoadjuvant treatment response prediction remain critical challenges in the management of locally advanced rectal cancer (LARC). The aim of this study was to investigate the clinical relevance of viable circulating tumor cells (CTCs) for DM or response in patients with LARC in a neoadjuvant setting. Methods The detection of viable CTCs at different stages of treatment was planned for consecutive patients from a prospective trial. The Kaplan–Meier method, Cox proportional hazards model, and logistic regression model were utilized to analyze factors associated with DM or pathological complete response (pCR) and clinical complete response (cCR). Results Between December 2016 and July 2018, peripheral blood samples from 83 patients were collected before any treatment (median follow‐up time, 49.3 months). CTCs were present in 76 of 83 patients (91.6%) at baseline, and more than three CTCs detected in the blood sample was considered high risk. Only the CTC risk group was significantly associated with 3‐year metastasis‐free survival (MFS) (high risk vs. low risk, 57.1% (95% CI, 41.6–72.6) vs. 78.3% (95% CI, 65.8–90.8), p = 0.018, log‐rank test). When all the important variables were entered into the Cox model, the CTC risk group remained the only significant independent factor for DM (hazard ratio (HR), 2.74; 95% CI, 1.17–6.45, p = 0.021). The pCR and continuous cCR rates were higher in patients with a decreased number of CTCs of more than one after radiotherapy (HR, 4.00; 95% CI, 1.09–14.71, P = 0.037). Conclusions The dynamic detection of viable CTCs may strengthen pretreatment risk assessment and postradiotherapy decision making for LARC. This observation requires further validation in a prospective study.

Abstract Background and Aims Colonoscopy is an important colorectal cancer (CRC) screening modality; however, not all high‐risk groups identified by fecal immunochemical test (FIT) and/or high‐risk factor questionnaire (HRFQ) undergo colonoscopy in time. The impact of delays in colonoscopy on CRC detection among high‐risk populations remains poorly understood, warranting further clarification. Methods A retrospective study was conducted among CRC high‐risk population identified by Tianjin CRC screening program. According to the colonoscopy results after HRFQ and FIT, patients were classified into CRC, advanced adenoma, non‐advanced adenoma, and normal groups. The time interval between CRC screening and colonoscopy was investigated and its relationship with colonoscopy results. Logistic regression was performed to explore the risk factors of CRC detection. Results Among the high‐risk population without a history of CRC or polyps, 49,810 underwent HRFQ, FIT, and colonoscopy, and a time interval of fewer than 6 months was found for 79.56% of patients (n = 39,630). People with positive FIT were more likely to undergo colonoscopy within 6 months, and detection rates of CRC and/or advanced adenoma were positively related to time intervals. Similar results were found in people with a negative FIT but positive HRFQ. A time interval longer than 6 months was a significant predictor of CRC detection in high‐risk populations. Conclusion For high‐risk people identified by CRC screening, especially those with a positive FIT, a time interval of 6 months was associated with an increased probability of CRC detection. Our findings emphasize that populations at high risk should undergo colonoscopy at least within 6 months.

To solve the ongoing problems of micro-alloyed Hadfield's steel, insufficient hardness and excessive deformation in the early working period, expensive alloying elements like Ti, Nb, and V have been utilized. However, traditional long-time, single-stage aging exacer-bates vanadium to assemble at the edge of initial precipitates, which diminishes estimated effects. For this, here we report the tremendous impact of retrogression and re-aging process (RRA) in this steel by booming the V (C, N) mean sized in 11 nm. The procedure enhances the micro-hardness, yielding strength, tensile strength, and impact-wear resistance for more than 27.4%, 29.5%, 22.2%, and 51.5%, respectively. Moreover, the wear mechanism of RRA samples has been investigated in that micro-sized precipitates surrounded by numerous nano V (C, N) stick in the matrix and hinder the abrasive embedding consistently, thus decreasing the micro-cutting and micro-plowing. This new process maximizes the utilization of costly and nonrenewable vanadium and magnifies the impact-wear resistance under either mild or medium-intensity working conditions.

Abstract Background Air pollution in China has raised great concerns due to its adverse effects on air quality, human health, and climate. Emissions of air pollutants (APs) are inherently linked with CO2 emissions through fossil-energy consumption. Knowledge of the characteristics of APs and CO2 emissions and their relationships is fundamentally important in the pursuit of co-benefits in addressing air quality and climate issues in China. However, the linkages and interactions between APs and CO2 in China are not well understood. Results Here, we conducted an ensemble study of six bottom-up inventories to identify the underlying drivers of APs and CO2 emissions growth and to explore their linkages in China. The results showed that, during 1980–2015, the power and industry sectors contributed 61–79% to China’s overall emissions of CO2, NOx, and SO2. In addition, the residential and industrial sectors were large emitters (77–85%) of PM10, PM2.5, CO, BC, and OC. The emissions of CH4, N2O and NH3 were dominated by the agriculture sector (46–82%) during 1980–2015, while the share of CH4 emissions in the energy sector increased since 2010. During 1980–2015, APs and greenhouse gases (GHGs) emissions from residential sources generally decreased over time, while the transportation sector increased its impact on recent emissions, particularly for NOx and NMVOC. Since implementation of stringent pollution control measures and accompanying technological improvements in 2013, China has effectively limited pollution emissions (e.g., growth rates of –10% per year for PM and –20% for SO2) and slowed down the increasing trend of carbon emissions from the power and industrial sectors. We also found that areas with high emissions of CO, NOx, NMVOC, and SO2 also emitted large amounts of CO2, which demonstrates the possible common sources of APs and GHGs. Moreover, we found significant correlations between CO2 and APs (e.g., NOx, CO, SO2, and PM) emissions in the top 5% high-emitting grid cells, with more than 60% common grid cells during 2010–2015. Conclusions We found significant correlation in spatial and temporal aspects for CO2, and NOx, CO, SO2, and PM emissions in China. We targeted sectorial and spatial APs and GHGs emission hot-spots, which help for management and policy-making of collaborative reductions of them. This comprehensive analysis over 6 datasets improves our understanding of APs and GHGs emissions in China during the period of rapid industrialization from 1980 to 2015. This study helps elucidate the linkages between APs and CO2 from an integrated perspective, and provides insights for future synergistic emissions reduction.

Abstract Background Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. Methods CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography‑derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). Results Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014–2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066–4.261; P = 0.032). Conclusion TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Abstract Background Bone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment. Methods We analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment. Results Here, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy. Conclusion Taken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis.

Abstract Introduction Gastroesophageal varices (GOV) bleeding is a common and serious complication of advanced liver cirrhosis with a median survival of less than 2 years. Multiple guidelines have pointed out that transjugular intrahepatic portosystemic shunt (TIPS) is the rescue treatment of acute variceal hemorrhage (AVB) after failure of standard therapy and an effective second-line treatment for preventing patients with high risks from rebleeding of GOV. The safety and stability of TIPS have been greatly improved due to the improvements of related technologies and the emergence of various novel devices, but the incidence of hepatic encephalopathy (HE) after shunting (10–50%) hindered the widespread use of TIPS. The target portal vein branch might affect the incidence of HE after TIPS. The aim of this study is to compare the rate of HE in patients with hepatitis B virus (HBV) related cirrhosis receiving TIPS either the left or right branch of the portal vein with 8mm Viatorr stent for preventing rebleeding from GOV. Methods and analysis This study is a multicenter randomized controlled trial comparing the influence of shunting left or right portal vein branch on post-TIPS hepatic encephalopathy for preventing rebleeding from GOV in patients with HBV-related cirrhosis. A total of 130 patients will be recruited over a period of 24 months across 5 centers in China. Eligible patients will be stratified 1:1 to constructing either a left or right portal vein shunt with an 8-mm Viatorr stent. The primary objective was to compare the incidence of post-TIPS hepatic encephalopathy between the two groups. The secondary objectives were to compare the grade and duration of hepatic encephalopathy, the rate of shunt dysfunction, the rate of variceal rebleeding, the HE-free survival, the cumulative patency rate of the stent, and the overall survival at 12 months and 24 months between two groups. Ethics and dissemination This study was approved by the ethics committee of Zhongshan Hospital of Fudan University (No. B2018-292R) and was registered at ClinicalTrials.gov (NCT03825848). All participants give written informed consent. Trial registration ClinicalTrials.gov NCT03825848. Registered on January 31, 2019 Trial status The first patient was recruited into our study on June 19, 2019. A total of 55 patients were recruited till May 27, 2021 (27 and 28 patients assigned to shunting the left (L Group) and right (R Group) branches of the portal vein, respectively).

Background: Coronavirus disease 2019(COVID-19) caused a large number of infections worldwide. Although some patients recovered from the disease, some of the other problems that accompanied it, such as cardiac injury, could affect the patient's subsequent quality of life and prognosis. Objectives: To clarify the molecular mechanism of cardiac injury in SARS-CoV-2 Infection. Methods: The RNA-Seq dataset (GSE184715) comparing expression profiling of Mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes(DEGs) were performed by the R software. Degs were analyzed by enrichment analysis to clarify the affected pathways. Hub genes were screened out by a PPI network constructed from Degs. Finally, Connectivity Map was used to screen for the treatment of COVID-19 induced cardiac injury. Results: 2705 differentially expressed genes were identified. Enrichment analysis confirmed that mitochondrial dysfunction was caused by SARS-CoV-2, meanwhile, cardiac muscle contraction was suppressed and NF-κB was activated. Based on the PPI network, 15 hub genes were identified. These 15 down-regulated hub genes were mainly involved in the reduced activity of complexes in the mitochondrial respiratory chain associated with mitochondrial dysfunction. Moreover, 5 candidate drugs were identified to treat cardiac injury. Conclusion: In conclusion, SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.

Abstract Background TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging. Results In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine. Conclusion TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.

Abstract Steatosis, as the early stage of nonalcoholic fatty acid disease (NAFLD), would progress into nonalcoholic steatohepatitis (NASH) and liver failure without intervention. Despite the development of animal models, there is still a lack of the human-relevant platform for steatosis modeling and drug & target discovery. Hendriks et al., reporting in Nature Biotechnology, leveraged human fetal liver organoids to recapitulate steatosis by introducing nutritional and genetic triggers. Using these engineered liver organoid-derived steatosis models, they screened drugs that alleviate steatosis, and mined common mechanism of effective compounds. Further, inspired by the results of drug screening, the arrayed CRISPR-LOF screening targeting 35 lipid metabolism genes was performed, and FADS2 was identified as a critical regulator of steatosis.

Elevated nitric oxide (NO) within tumor-associated macrophages (TAMs) suggests a reduction of TAM-mediated tumoral immune tolerance. This cellular event could be a reliable indicator for efficacy evaluation of antineoplastic drugs. However, a suitable method for TAM-specific NO measurement is still lacking. In this work, a simple and fast efficacy evaluation method for antineoplastic drugs is established based on a ratiometric TAM-specific NO near-infrared (NIR) fluorescence probe TAM-Cy-NO. Molecular fluorescence probe Cy-NO for NO response was encapsulated in the TAM-targeting peptide (M2pep)-functionalized liposome to construct TAM-Cy-NO. After TAM enters through M2pep, Cy-NO reacts with NO specifically, resulting in a dose-dependent ratiometric fluorescence signal (I610/I815) change manner. Utilizing this strategy, we observed that PLX-3397, metformin, and ibrutinib triggered NO generation within TAM greater than that with sorafenib. Notably, metformin and ibrutinib promoted TNF-α and reduced PD-L1 expressions, which suggest reductions of TAM-mediated immunosuppression. As expected, these drugs delayed tumor progression in mice. This method provides a promising efficacy evaluation strategy for rapid screening of antineoplastic drugs.

Abstract Objectives The gut virome of humans is mainly composed of bacteriophages and their role in shaping the gut microbiome and influencing human health is increasingly recognized. However, little is known about the dynamic changes of the gut virome in children and its role in growth and development. In this study, we collected fecal samples from newborns and children under 5 years old from the same area during the same time period to investigate the gut viral community using viral metagenomic technique. Methods We used viral metagenomics to compare the gut bacteriophage composition between newborns and children under 5 years of age. We collected fecal samples from 45 newborns who were born at the Affiliated Hospital of Jiangsu University and 45 healthy children who were examined at the same hospital. The two groups were classified as the newborn group and the children group. Results Our sequencing analysis showed that the number of seqeunce reads of the children group were more than that of the newborn group. The results of alpha diversity and beta diversity both indicated that the diversity of the children group was significantly higher than that of the newborn group and the children group is different from the newborn group. The abundance of gut virome in the children group was also higher than that in the newborn group. The analysis of the genetic characteristics of the viruses showed that the phage genome was scattered and clustered with specificity. Conclusion Our findings indicate that the gut bacteriophage communities undergo changes over time, presenting diversity and dynamic characteristics. We characterized the composition of gut virome in children and newborns in this region. However, further research is needed to investigate the function of bacteriophages in the ecology of the gastrointestinal tract.

Abstract The difficulty of degrading lignin is the main factor limiting the high-value conversion process of lignocellulosic biomass. The biodegradation of lignin has attracted much attention because of its strong environmental friendliness, but it still faces some dilemmas such as slow degradation rate and poor adaptability. The microbial consortia with high lignin degradation efficiency and strong environmental adaptability were obtained in our previous research. To further increase the lignin degradation efficiency, this paper proposes a composite treatment technology of steam explosion combined with microbial consortium degradation to treat three kinds of biomass. We measured the lignin degradation efficiency, selectivity value (SV) and enzymatic saccharification efficiency. The structural changes of the biomass materials and microbial consortium structure were also investigated. The experimental results showed that after 1.6 MPa steam explosion treatment, the lignin degradation efficiency of the eucalyptus root reached 35.35% on the 7th days by microbial consortium. At the same time, the lignin degradation efficiency of the bagasse and corn straw treated by steam explosion followed by microbial biotreatment was 37.61–44.24%, respectively, after only 7 days of biotreatment. The microbial consortium also showed strong selectivity degradation to lignin. The composite treatment technology can significantly improve the enzymatic saccharification efficiency. Saccharomycetales, Ralstonia and Pseudomonadaceae were the dominant microorganisms in the biomass degradation systems. It was proved that the combined treatment technology of steam explosion and microbial consortium degradation could overcome the drawbacks of traditional microbial pretreatment technology, and can facilitate the subsequent high-value conversion of lignocellulose.

Abstract Background Neuropsychiatric involvement is one of the major concerns in systemic lupus erythematosus (SLE). The therapeutic effect of intrathecal treatment of methotrexate and dexamethasone has been investigated in some exploratory studies, but its influence on the long-term prognosis of neuropsychiatric SLE (NPSLE) remains unknown. Methods This was a propensity score-matched retrospective study. Outcomes at discharge and time free from NPSLE relapse or death were evaluated by multivariate logistic regression, survival analysis, and Cox regression as appropriate. Results Among 386 hospitalized patients with NPSLE, the median [IQR] age was 30.0 [23.0–40.0] years, and 342 patients (88.4%) were female. Of those, 194 patients received intrathecal treatment. Patients in the intrathecal treatment group had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores (median 17 vs. 14 points, IQR 12–22 vs. 10–19 points, P

Abstract Background Porcine circovirus type 2 (PCV2) has caused great economic losses in the global pig industry. There have been published records of wild rats acting as the reservoirs of PCV2 (only PCV2a and PCV2b), but almost all of which were related to the PCV2-infected swine herds. Results In this study, we carried out the detection, amplification, and characterization of novel PCV2 strains in wild rats that were captured far from pig farms. Nested PCR assay demonstrated that the kidney, heart, lung, liver, pancreas, and large and small intestines of rats were screened positive for PCV2. We subsequently sequenced two full genomes of PCV2 in positive sample pools, designated as js2021-Rt001 and js2021-Rt002. Genome sequence analysis indicated that they had the highest similarity to nucleotide sequences of porcine-origin PCV2 isolates in Vietnam. Phylogenetically, js2021-Rt001 and js2021-Rt002 were a part of the PCV2d genotype cluster, which is a predominant genotype circulating worldwide in recent years. The antibody recognition regions, immunodominant decoy epitope, and heparin sulfate binding motif of the two complete genome sequences coincided with those previously reported. Conclusions Our research reported the genomic characterization of two novel PCV2 strains (js2021-Rt001 and js2021-Rt002) and provided the first supported evidence that PCV2d could naturally infect wild rats in China. However, whether the newly identified strains have potential for circulating in nature in vertical and horizontal transmission or inter-species jumping between rats and pigs needs further research.