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Zhanjie Li,1,* Jian Li,2,* Chuanlong Zhu,3 Shengyuan Jiao1,2 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Disease Prevention and Control, Air Force Hospital of Eastern Theater, Nanjing, People’s Republic of China; 3Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengyuan Jiao, Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8618021136781, Email 17319884906@163.com Chuanlong Zhu, Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +8617714316539, Email zhuchuanlong@jsph.org.cnBackground: To identify risk factors for acquiring HAIs in COVID-19 patients and establish visual prediction model.Methods: Data was extracted from Xinglin Hospital Infection Monitoring System to analyze COVID-19 patients diagnosed between December 1, 2022, and March 1, 2023. Univariate and multivariate analyses were conducted to identify risk factors. Predictive signature was developed by selected variables from lasso, logistic regression, and their intersection and union. Models were compared using DeLong’s t-tests. Likelihood ratio (LR) and Youden’s index was used to evaluate the predictive performance. Nomogram was constructed using optimal variables ensemble, prediction accuracy was evaluated using AUC, DCA and calibration curve.Results: Total of 739 patients met the criteria, of which 53 (7.2%) were HAIs. NSAIDs, surgery, fungi and MDRO detected, hormone drugs and LYMR were independent risk factors. Lasso model screened seven variables, and logistic model identified six risk factors. Union model performed the best with the maximum of the Youden’s index is 0.703, the sensitivity is 95.6%, the specificity is 74.7%, the LR is 3.778. The best AUC of union model is 0.953 (0.928– 0.978), and the accuracy is 87.5%. DCA indicated that the union model provided the best net benefits and calibration curve demonstrated good predictive agreement.Conclusions: HAIs prediction in COVID-19 patients is feasible and beneficial to improve prognosis. Physicians can use this nomogram to identify high-risk COVID-19 populations for HAIs and tailor follow-up strategies.Keywords: risk factors, healthcare-associated infection, COVID-19, nomogram, prediction model

Ke Li,1,2,* Lupeng Qiu,1,2,* Yang Zhao,3,* Xiaohui Sun,1,2 Jiakang Shao,1 Chang He,1,2 Boyu Qin,4 Shunchang Jiao4 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Vascular Intervention, Special Medical Center for Strategic Support Forces, Beijing, 100101, People’s Republic of China; 4Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunchang Jiao; Boyu Qin, Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, 8 Dongdajie Street, Fengtai District, Beijing, 100071, People’s Republic of China, Email jiaosc@vip.sina.com; qpm2017@126.comPurpose: This study aims to investigate the process of small cell lung cancer (SCLC) patients from achieving optimal efficacy to experiencing disease progression until death. It examines the predictive value of the treatment response on progression free survival (PFS) and overall survival (OS) of SCLC patients.Patients and Methods: We conducted a retrospective analysis on 136 SCLC patients diagnosed from 1992 to 2018. Important prognostic factors were identified to construct nomogram models. The predictive performance of the models was evaluated using the receiver operating characteristic curves and calibration curves. Survival differences between groups were compared using Kaplan–Meier survival curves. Subsequently, an independent cohort consisting of 106 SCLC patients diagnosed from 2014 to 2021 was used for validation.Results: We constructed two nomograms to predict first-line PFS (PFS1) and OS of SCLC. The area under the receiver operating characteristic curves for the PFS1 nomogram predicting PFS at 3-, 6-, and 12-months were 0.919 (95% CI: 0.867– 0.970), 0.908 (95% CI: 0.860– 0.956) and 0.878 (95% CI: 0.798– 0.958), and for the OS nomogram predicting OS at 6-, 12-, and 24-months were 0.814 (95% CI: 0.736– 0.892), 0.819 (95% CI: 0.749– 0.889) and 0.809 (95% CI: 0.678– 0.941), indicating those two models with a high discriminative ability. The calibration curves demonstrated the models had a high degree of consistency between predicted and observed values. According to the risk scores, patients were divided into high-risk and low-risk groups, showing a significant difference in survival rate. And these findings were validated in another independent validation cohort.Conclusion: Based on the patients’ treatment response after standardized treatment, we developed and validated two nomogram models to predict PFS1 and OS of SCLC. The models demonstrated good accuracy, reliability and clinical applicability by validating in an independent cohort.Keywords: small cell lung cancer, treatment response, patient prognosis, nomogram prognostic model

Jieqiong Liu,1 Rongge Xing,2 Jiakang Shao,1 Shunchang Jiao1,3 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Cangzhou Central Hospital, Cangzhou, Hebei Province, 061000, People’s Republic of China; 3Department of Oncology, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Shunchang Jiao, Department of Oncology, the First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email jiaosc301@163.comBackground: Recurrent metastasis after radical resection in patients of colorectal cancer (CRC) is a great challenge for the world, in which genomic alterations play a major role in tumorigenesis. MUC4 plays a significant role in recurrence and metastasis in tumor. This study is aimed at exploring the association between MUC4 variants and metastatic recurrence of CRC.Methods: Forty-seven patients relapsing with metastasis and 37 patients remaining disease‐free postoperatively were enrolled. Next-generation sequencing (NGS) detected mutations. Mutation and mRNA expression data were downloaded from TCGA and cBioPortal databases. We analyzed the relationship between MUC4 variants and clinical parameters, as well as possible molecular mechanisms.Results: MUC4 variants rs56359992 and rs781124621 were associated with survival in patients with CRC. Rs56359992 was more common in patients with metastatic recurrence. MAPK pathway, PI3K-Akt pathway, JAK-STAT pathway, cell cycle, WNT pathway and mTOR pathway were found to correlate with MUC4 mutation by GO/KEGG analysis, as well as resting and activated mast cell related to MUC4 mutation by CIBERSORT analysis.Conclusion: Genetic variants of MUC4 with CRC may constitute a molecular signature of metastatic recurrence. MUC4 may become a new target for the treatment of CRC recurrence.Keywords: colorectal cancer, MUC4, recurrence, next-generation sequencing

Junyan Chen,1,2,* Wuyan Xu,2,* Tianming Dai,3,* Songsong Jiao,2 Xiang Xue,2 Jiayang Jiang,1,2 Siming Li,1,3 Qingqi Meng3 1Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2Department of Orthopaedics, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People’s Republic of China; 3Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People’s Republic of China*These authors contributed equally to this workCorrespondence: Siming Li; Qingqi Meng, Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, People’s Republic of China, Tel +8613929526981, Email drsmli@163.com; mengqingqi@jnu.edu.cnBackground: Hyaluronic acid (HA) is a popular biological material for osteoarthritis (OA) treatment. Pioglitazone, a PPAR-γ agonist, has been found to inhibit OA, but its use is limited because achieving the desired local drug concentration after administration is challenging.Purpose: Herein, we constructed HA-based cartilage-targeted nanomicelles (C-HA-DOs) to deliver pioglitazone in a sustained manner and evaluated their efficacy in vitro and in vivo.Methods: C-HA-DOs were chemically synthesized with HA and the WYRGRL peptide and dodecylamine. The products were characterized by FT-IR, 1H NMR, zeta potential and TEM. The drug loading rate and cumulative, sustained drug release from Pio@C-HA-DOs were determined, and their biocompatibility and effect on oxidative stress in chondrocytes were evaluated. The uptake of C-HA-DOs by chondrocytes and their effect on OA-related genes were examined in vitro. The nanomicelle distribution in the joint cavity was observed by in vivo small animal fluorescence imaging (IVIS). The therapeutic effects of C-HA-DOs and Pio@C-HA-DOs in OA rats were analysed histologically.Results: The C-HA-DOs had a particle size of 198.4± 2.431 nm, a surface charge of − 8.290± 0.308 mV, and a critical micelle concentration of 25.66 mg/Land were stable in solution. The cumulative drug release from the Pio@C-HA-DOs was approximately 40% at pH 7.4 over 24 hours and approximately 50% at pH 6.4 over 4 hours. Chondrocytes rapidly take up C-HA-DOs, and the uptake efficiency is higher under oxidative stress. In chondrocytes, C-HA-DOs, and Pio@C-HA-DOs inhibited H2O2-induced death, reduced intracellular ROS levels, and restored the mitochondrial membrane potential. The IVIS images confirmed that the micelles target cartilage. Pio@C-HA-DOs reduced the degradation of collagen II and proteoglycans by inhibiting the expression of MMP and ADAMTS, ultimately delaying OA progression in vitro and in vivo.Conclusion: Herein, C-HA-DOs provided targeted drug delivery to articular cartilage and improved the role of pioglitazone in the treatment of OA.Keywords: nanoparticles, micelles, drug delivery, hyaluronic acid, knee joint

Shicheng Jiao,1,* Mu Niu,2,* Jie Yang2 1Jiao Shicheng Medical Beauty Clinic, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Yang, Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China, Email 13337564169@163.comAbstract: A 53-year-old male presented to the clinic for “bilateral temporal dark yellow plaques with pruritus for 8 years.” The patient had bilateral temporal dark yellow plaques without obvious inducement 8 years ago and did not see doctors at that time. Five years ago, bilateral temporal skin lesions gradually increased and were accompanied by severe itching. On top of them, there were several blackheads and pimples with the size of needle tips up to the size of rice grains. After compression, lipid substances could be excreted and there was a clear odor. The patient sought medical attention at a local hospital, but the diagnosis and medication were unknown, and the symptoms did not improve. In the past month, due to the aggravation of skin lesions and itching that affected sleep, he visited the outpatient clinic of our hospital again. The patient was diagnosed with nodular elastoidosis with cysts and acne and was given 5% peroxybenzoyl gel and 0.1% tretinoin cream for topical use. After 2 weeks, the itching symptoms of the patient were significantly reduced.Keywords: nodular elastoidosis, cysts, acne

Shuyue Jiao,1 Xin Zhang,2 Dapeng Wang,3 Hongyong Fu,3 Qingxin Xia3 1Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University; Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou, People’s Republic of ChinaCorrespondence: Qingxin Xia; Hongyong Fu, Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University; Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou Key Laboratory of Accurate Pathological Diagnosis of Intractable Tumors, Zhengzhou, 450000, People’s Republic of China, Email tudou414135404@163.com; dlxiaoyong@126.comIntroduction: Small cell lung cancer (SCLC), an aggressive subtype of lung cancer characterized by the development of neuroendocrine tumors, is prone to distant metastasis, resistant to platinum-based drugs and has a poor prognosis. The development of next-generation sequencing technology (NGS) has led to the identification of many genetic alterations in SCLC. Few druggable targeted molecules can be used in clinical practice. Currently, NGS is widely employed in routine clinical practice of non-small cell lung cancer to assist in therapeutic options and prognosis evaluation. This study aims to investigate genes involved in small cell lung cancer (SCLC), their occurrence and their significance in clinical events.Methods: Tumor tissue specimens from 18 Chinese SCLC patients were collected through a 520 cancer‐related genes panel for next-generation sequencing. First, the association between sequence results and clinical outcomes was examined. Subsequently, data on clinical pathology and sequencing results were analyzed.Results: The Kaplan–Meier curve displayed a significant reduction in PFS for SCLC patients with LRP1B or MAP3K13 mutations. Overall survival (OS) of SCLC patients with MSH6 mutation was significantly higher than those with SPEN mutation.Conclusion: Next-generation sequencing demonstrates that the genetic landscape of SCLC. Mutation status of LRP1B, MAP3K13, MSH6 and SPEN has prognostic significance, which might be potential therapeutic targets. We found possible genes and related signaling pathways that affect metastasis. These results can improve our understanding of the mutation characteristics of SCLC and identify potential biomarkers to guide targeted therapies.Keywords: small cell lung cancer, next-generation sequencing, genetic alteration, tumor mutation burden, clinical significance

Siyuan Li,* Siqi Jiao,* Siwei Zhang,* Jiangjiao Zhou Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiangjiao ZhouDepartment of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaEmail zhoujiangjiao@csu.edu.cnAbstract: Bariatric surgery has become increasingly common due to the worldwide obesity epidemic. A shift from open to laparoscopic surgery, specifically, laparoscopic sleeve gastrectomy (LSG), has occurred in the last two decades because of the low morbidity and mortality rates of LSG. Although LSG is a promising treatment option for patients with morbid obesity due to restrictive and endocrine mechanisms, it requires modifications for a subset of patients because of weight regain and tough complications, such as gastroesophageal reflux, strictures, gastric leak, and persistent metabolic syndrome., Revision surgeries have become more and more indispensable in bariatric surgery, accounting for 7.4% in 2016. Mainstream revisional bariatric surgeries after LSG include Roux-en-Y gastric bypass, repeated sleeve gastrectomy, biliopancreatic diversion, duodenal switch, duodenal-jejunal bypass, one-anastomosis gastric bypass, single anastomosis duodeno-ileal bypass (SAID) and transit bipartition. This review mainly describes the revisional surgeries of LSG, including the indication, choice of surgical method, and subsequent effect.Keywords: bariatric surgery, laparoscopic sleeve gastrectomy, revisional surgery

Heng Liu,1 Tijiang Zhang,1 Song Jiao,2 Bangguo Li,1 Jing Guan,1 Yi-Xiang J Wang3 1Department of Radiology, 2Cerebrovascular Diseases Clinic, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 3Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People’s Republic of China Background: The purpose of this study was to investigate the epidemiology of sporadic ruptured cerebral aneurysm in the Chinese population. Methods: We retrospectively analyzed the medical records of 264 consecutive Chinese patients admitted to the Affiliated Hospital of Zunyi Medical University of Guizhou Province in Southwest China between December 2012 and March 2015 for spontaneous subarachnoid hemorrhage due to a ruptured cerebral artery aneurysm.Results: The study population comprised 171 females and 93 males with a median age of 50 (range 5–76) years. The female to male ratio was 1.84:1. For both males and females, aneurysm rupture was most common in the 40–49-year age group (34.5%). Most of the ruptured aneurysms were in the size range of 2–5 mm (47.2%), followed by 5–10 mm (43.8%). Ruptured aneurysms occurred most often in the posterior communicating artery (36.6%) or the anterior communicating artery (25.7%). There were more cases of anterior communicating artery aneurysm on the left side (53 [Left side]/16 [Right side]=3.31, P0.05).Conclusion: This study provides valuable information on the epidemiology of ruptured cerebral aneurysm in the Chinese population. Keywords: cerebral aneurysm, rupture, subarachnoid hemorrhage, Chinese population, epidemiology

The energy crisis and environmental pollution pose great challenges to human development. Traditional vapor-compression cooling consumes abundant energy and leads to a series of environmental problems. Radiative cooling without energy consumption and environmental pollution holds great promise as the next generation cooling technology, applied in buildings mostly in indirect way. In this work, a temperature-regulating module was introduced for direct summer cooling and winter heating. Firstly, the summer experiments were conduct to investigate the radiative cooling performance of the module. And the results indicated that the maximum indoor temperature reached only 27.5 °C with the ambient temperature of 34 °C in low latitude areas and the air conditioning system was on for only about a quarter of the day. Subsequently, the winter experiments were performed to explore the performance of the module in cooling and heating modes. The results indicated that indoor temperature can reach 25 °C in the daytime without additional heat supply and about a quarter of the day didn't require heating in winter. Additionally, the transient model of the module and the building revealed that the electricity saving of 42.4% (963.5 kWh) can be achieved in cooling season with the module, and that was 63.7% (1449.1 kWh) when coupling with energy storage system. Lastly, further discussion about the challenges and feasible solutions for radiative cooling to directly combine with the buildings were provided to advance the application of radiative cooling. Furthermore, with an acceptable payback period of 8 years, the maximum acceptable incremental cost reached 26.2 $/m2. The work opens up a new avenue for the application mode of the daytime radiative cooling technology.

Both tea polyphenols (TP) and Lactobacillus rhamnosus have been shown to alleviate obesity, and regulate lipid metabolism. However, the combined effects and their underlying mechanisms of action remain elusive. In the present work, the effects of TP, Lactobacillus rhamnosus R5 (R5), and TP+R5 on blood lipids and the gut microbiota of mice fed with a high-fat diet were compared. Results showed that the combination of TP and R5 effectively increased the serum levels of high-density lipoprotein cholesterol (HDL-C), and decreased total cholesterol (TC) levels, low-density lipoprotein cholesterol (LDL-C) levels, and the atherosclerosis index (AI) in mice fed with a high-fat diet. The combination treatment resulted in a modification of the structure of the gut microbiota in mice, as evidenced by a decrease in the F/B ratio, and an increase in the abundance of beneficial genera, such as Akkermansia muciniphila, Faecalibaculum rodentium, and Ruminococcus_uncultured bacterium. Additionally, the contents of SCFAs (acetic, propionic, and butyric acids) in faeces also increased. These could provide new ideas for anti-obesity methods, and a theoretical basis for the development of foods combining probiotics and tea polyphenols. [ABSTRACT FROM AUTHOR]

Abstract Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C-terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome.

Abstract Two-dimensional (2D) multiferroic materials are recognized as promising candidates for next-generation nanodevices due to their tunable magnetoelectric coupling and distinctive physical phenomena. In this study, we proposed a novel 2D multiferroic van der Waals heterostructure (vdWH) by stacking atomic layers of ferroelectric In2Se3 and ferromagnetic MnI3. Using first-principles calculations, we found that the MnI3/In2Se3 vdWH exhibit robust metallic conductivity across various spin and polarization states, preserving the distinctive band characteristics of isolated In2Se3 and MnI3. However, the alignment of Fermi levels causes the conduction band minimum (CBM) and valence band maximum (VBM) of In2Se3 and MnI3 to shift relative to their original band structures. Remarkably, the MnI3/In2Se3 with the upward polarization state of In2Se3 exhibits an Ohmic contact. Switching the polarization direction of In2Se3 from upward to downward can transform the MnI3/In2Se3 vdWH from an Ohmic contact to a p-type Schottky contact, while also modifying its dipole moment, magnetic strength and direction. Based on these properties of MnI3/In2Se3 vdWH, we designed the field-effect transistors (FETs) with high on/off rates and nonvolatile data storage device. Furthermore, the Schottky barrier heights (SBHs), magnetic moment, and dipole moment of MnI3/In2Se3 vdWH can also be effectively regulated by reducing the interlayer distance. With the continuous reduction of the interlayer distance of MnI3/In2Se3 vdWH, its easy magnetization axis is expected to shift from in-plane to out-of-plane. These findings offer new insights for the design and development of the next-generation spintronic and nonvolatile memory nanodevices.

Abstract Ovalbumin (OVA) in egg is one of the predominant causes of food allergy around the world. In the present study, the alleviating effect of selenium‐enriched tea polysaccharide (Se‐TPS) on OVA allergy was evaluated, and the underlying mechanistic insights were investigated. Se‐TPS significantly alleviated the clinical manifestations and diarrhea of allergic mice, accelerated the recovery of jejunal injury, and decreased the immune organ index. Meanwhile, Se‐TPS decreased the levels of immunoglobulin E (IgE), histamine, and IL‐4 in serum, increased the levels of IFN‐γ, and promoted the balance of Th1/Th2 cells. Furthermore, the intervention of Se‐TPS reshaped the gut microbiota structure of OVA‐allergic mice. Se‐TPS increased the abundance of Lachnospiraceae_NK4A136_group, unclassified_f_Lachnospiraceae, and Alistipes, whereas decreased the Faecalibaculum abundance. Analysis of intestinal metabolites showed that Se‐TPS treatment caused a significant increase in homocitrulline and 7a‐hydroxyandrost‐4‐ene‐3,17‐dione levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment results indicated that Se‐TPS treatment may alleviate allergic symptoms by enhancing the anti‐inflammatory ability of OVA‐allergic mice through neuroimmunity.

Abstract Immune checkpoint blockade (ICB) therapies function by alleviating immunosuppression on tumor-infiltrating lymphocytes (TILs) but are often insufficient to fully reactivate these dysfunctional TILs. Although interleukin 12 (IL-12) has been used in combination with ICB to improve efficacy, this remains limited by severe toxicity associated with systemic administration of this cytokine. Here, we engineer a fusion protein composed of an anti-PD-1 antibody and a mouse low-affinity IL-12 mutant-2 (αPD1-mIL12mut2). Systemic administration of αPD1-mIL12mut2 displays robust antitumor activities with undetectable toxicity. Mechanistically, αPD1-mIL12mut2 preferentially activates tumor-infiltrating PD-1+CD8+T cells via high-affinity αPD-1 mediated cis-binding of low-affinity IL-12. Additionally, αPD1-mIL12mut2 treatment exerts an abscopal effect to suppress distal tumors, as well as metastasis. Collectively, αPD1-mIL12mut2 treatment induces robust systemic antitumor responses with reduced side effects.

ABSTRACT: The current study investigated the effects of dietary crude protein (CP) level on the liver lipid metabolism, gut microbiota, and bile acids (BA) profiles of growing pullets. Roman growing pullets (N = 180, 13-wk-old) were divided into 3 treatments groups with 6 replicates in each group and 10 hens in each replicate and provided 3 different dietary CP level diet treatments. The diet treatments included: a high-protein diet (15.5% CP, HP group), a medium-protein diet (14.5% CP, MP group), and a low-protein diet (13.5% CP, LP group). Compared with HP group, LP group significantly increased the lipid contents in the body (such as Breast intramuscular fat [BIMF], Leg intramuscular fat [LIMF], Percentage of abdominal fat [PAF], liver triglyceride [TG] and liver cholesterol [TC]), and the lipid metabolism-related parameters in serum (such as cholesterol (TC), high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low density lipoprotein [VLDL]), and the mRNA expression of lipid metabolism-related genes (such as fatty acid synthase [FAS], CCAAT/enhancer binding protein β [C/EBPβ], and fatty acid translocase [FAT/CD6]) (P < 0.05). In addition, LP group significantly reduced the contents of lithocholic acid (LCA), isoLCA, and ursodesoxycholic acid (UDCA), and increased the deoxycholic acid (DCA) content compared with HP group (P < 0.05). The effects of LCA on lipid deposition were confirmed in chicken preadipocyte cell line (CPI), in which LCA supplementation significantly decreased the relative expression of PPARγ, FAS, acyl-CoA carboxylase (ACC) and SREBP-1c (P < 0.05). Correlation analysis further revealed a significant association between BA profiles and lipid metabolism-related parameters. Furthermore, 16S rRNA gene sequencing indicated that dietary protein level can significantly affect the richness, diversity, and composition of cecal microbiota in growing pullets. LP group significantly increased the abundance of Bacteroidetes and significantly decreased the abundance of Firmicutesa compared with the HP group. In summary, low protein diet in growing pullets influence the liver lipid metabolism through changing the gut microbiota and liver BA metabolism.

Gas adsorption and separation/desorption are two pivotal stages in gas capture, demanding additional energy for liberating gas molecules from the adsorbent. Hence, it’s essential to engineer an adsorbent with minimal energy consumption yet effective gas adsorption–desorption characteristics. Accordingly, this research introduces a carbon nano-network (CNN) material capable of inhaling and exhaling gases via self-deformation. Molecular dynamics simulations demonstrate that the gas adsorption–desorption capabilities of CNN can be efficiently regulated by its deformation. While the size of CNN minimally affects the gas sorption rate, a larger CNN necessitates a prolonged duration to achieve saturation under identical gas conditions. Incorporating elongated appendages in CNN enhances both its stability during contraction and its efficiencies in gas adsorption and desorption. We discerned that attaining a critical gas density within a confined space is imperative to initiate self-desorption of CNN. Specifically, if the gas density dips below this critical threshold–set at 5.2 times that of CO2 at room temperature (300 K) and atmospheric pressure (1 Bar)–CNN exhibits no self-desorption capability. Nevertheless, even a marginal elevation in gas density triggers and maintains self-desorption with a consistently surpassing desorption ratio of 98 %. This discovery offers valuable insights for designing automatic self-desorption materials or apparatuses.

After hunting, predators tend to leave a large amount of carrion behind. It is widely reported that this resource is commonly used by various species in the ecosystem and is essential for the survival of scavengers, particularly in winter. Although recent studies are focused on mammals, little is known about how this works with facultative scavenger birds, which may lead to a serious underestimation of the key role that top predators such as the Amur tiger (Panthera tigris altaica) play in ecosystems. Here, we conducted a field feeding experiment to quantitatively evaluate the effects of Amur tiger on avian scavengers by simulating their predation residue. The results show that the Corvidae is the main bird species that consumes carrion, while woodpeckers and some insectivorous songbirds also benefit from the remains that Amur tiger leaves behind. We assumed that in winter, if the daily energy demand for the six main scavenger birds completely relied on the predation residues of Amur tiger separately, the prey remains of one Amur tiger could feed about 28 crows, 49 Azure-winged magpies, 61 Eurasian jays, 235 Eurasian nuthatches, 96 Great spotted woodpeckers, or 385 Willow tits. It means that the prey remains of top predators like Amur tiger may be an extremely important resource to avian scavengers and carrion could be a potential ecological indicator of Amur tiger keystone effect. This study provides experimental evidence from the field for the first time, and reveals the ecological mechanism of the role of keystone species of the Amur tiger, i.e., how to indirectly protect other animal groups in the forest ecosystem that have important ecological value for the biodiversity and the health of local forest vegetation through the protection of the Amur tiger.

[Objective] In order to investigate the effects of mushroom residue organic fertilizer and desulfurized gypsum on organic carbon components and carbon pool management index (CPMI) of saline-alkali soil. [Methods] The newly reclaimed wheat-maize rotation land in the Yellow River Delta was used as the research subject, and the randomized block experiment method was conducted to set up four treatments: no fertilization (CK), conventional farming fertilization (CN), mushroom residue organic fertilizer (MCOF), mushroom residue organic fertilizer and desulfurized gypsum (MCOG), which were treated by field fertilization for 3 years. [Results] The combined application of mushroom residue organic fertilizer and desulfurized gypsum significantly reduced the salinity of 0—20 cm soil layer, and increased the soil nitrogen, phosphorus and potassium nutrition content and cation exchange capacity (p

Abstract Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .

Manipulating the thermal emission in the infrared (IR) range significantly impacts both fundamental scientific research and various technological applications, including IR thermal camouflage, information encryption, and radiative cooling. While prior research has put forth numerous materials and structures for these objectives, the significant challenge lies in attaining spatially resolved and dynamically multilevel control over their thermal emissions. In this study, a one-step ultrafast laser writing technique is experimentally demonstrated to achieve position-selective control over thermal emission based on the phase-change material Ge2Sb2Te5 (GST). Ultrafast laser writing technique enables direct fabrication and manipulation of laser-induced crystalline micro/nano-structures on GST films. Thermal emission can be precisely controlled by adjusting the pulse energy of the ultrafast laser, achieving a high thermal emissivity modulation precision of 0.0014. By controlling thermal emission, the ultrafast laser writing technique enables multilevel patterned processing. This provides a promising approach for multilevel IR thermal camouflage, which is demonstrated with emissivity-modulated GST emitters. Remarkably, ultrafast laser-induced crystalline micro/nano-structures display geometric grating features, resulting in a diffraction-based structural color effect. This study demonstrates the effective use of laser-printed patterns for storing information in both visible and infrared spectrum.