DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors

Objective Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors. Methods To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR. Results The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo. Conclusion In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future (AU)

Calponin 2 regulates ketogenesis to mitigate acute kidney injury.

Calponin 2 (CNN2) is a prominent actin stabilizer. It regulates fatty acid oxidation (FAO) by interacting with estrogen receptor 2 (ESR2) to determine kidney fibrosis. However, whether CNN2 is actively involved in acute kidney injury (AKI) remains unclear. Here, we report that CNN2 was induced in human and animal kidneys after AKI. Knockdown of CNN2 preserved kidney function, mitigated tubular cell death and inflammation, and promoted cell proliferation. Distinct from kidney fibrosis, proteomics showed that the key elements in the FAO pathway have few changes during AKI, but we identified that 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2), a rate-limiting enzyme of endogenous ketogenesis that promotes cell self-renewal, was markedly increased in CNN2 knockdown kidneys. The ketone bodies ß-hydroxybutyrate and ATP production were increased in CNN2 knockdown mice. Mechanistically, CNN2 interacts with ESR2 to negatively regulate activities of mitochondrial sirtuin 5. Activated sirtuin 5 subsequently desuccinylates Hmgcs2 to produce energy for mitigating AKI. Understanding CNN2-mediated discrete fine-tuning of protein posttranslational modification is critical to optimize organ performance after AKI.

Influencing of serum inflammatory factors on IVF/ICSI outcomes among PCOS patients with different BMI.

Introduction: Overweight and obese are important factors leading to the occurrence of long-term complications in women with polycystic ovary syndrome (PCOS). There has been controversy over whether dissatisfaction with pregnancy outcomes in PCOS patients is influenced by chronic inflammatory status or obesity. This retrospective study analyzed the levels of inflammatory factors in PCOS patients with different body mass index (BMI) groups and effective predictors of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancy outcomes. Methods: There were 273 women with PCOS diagnosed who completed serum inflammatory factors test between January 2017 and June 2022 were selected. The data of 7,649 infertility PCOS patients who received their first IVF/ICSI treatment in the Reproductive Center of Peking University Third Hospital during the period of the study were collected. Finally, 92 PCOS patients were included in the high BMI group, while 97 patients were included in the normal BMI group. Baseline characteristics were collected and the pregnancy outcomes were compared among the two groups. Then, serum inflammatory factors' effect on IVF/ICSI pregnancy outcomes were analyzed with age, anti-Mullerian Hormone (AMH) and BMI adjusted. Results: PCOS patients in the high BMI group significantly had a lower number of oocytes retrieved and good quality embryos. The high BMI group PCOS patients had higher levels of IL-6 and lower cumulative clinical pregnancy and live birth rates. The level of GM-CSF was higher in the first cycle transfer and cumulative miscarriage group. High TNF-α was negatively correlated with the first transfer cycle and cumulative clinical pregnancy rates after age, AMH and high BMI adjusted. In addition, the cumulative live birth rate was negatively correlated with high IL-6, but the first cycle transfer and cumulative live birth rates were positively correlated with high IL-1ß. Discussion: For PCOS patients, in addition to BMI, attention should also be paid to inflammatory indicators. High levels of TNF-α and IL-6 were negatively correlated with pregnancy outcomes, but high IL-1ß was positively correlated with live birth rates among PCOS patients. The level of GM-CSF was higher in miscarriage PCOS patients.

Deciphering transcriptomic determinants of the divergent link between PD-L1 and immunotherapy efficacy.

Programmed cell death ligand 1 (PD-L1) expression remains the most widely used biomarker for predicting response to immune checkpoint inhibitors (ICI), but its predictiveness varies considerably. Identification of factors accounting for the varying PD-L1 performance is urgently needed. Here, using data from three independent trials comprising 1239 patients, we have identified subsets of cancer with distinct PD-L1 predictiveness based on tumor transcriptome. In the Predictiveness-High (PH) group, PD-L1+ tumors show better overall survival, progression-free survival, and objective response rate with ICI than PD-L1- tumors across three trials. However, the Predictiveness-Low (PL) group demonstrates an opposite trend towards better outcomes for PD-L1- tumors. PD-L1+ tumors from the PH group demonstrate the superiority of ICI over chemotherapy, whereas PD-L1+ tumors from the PL group show comparable efficacy between two treatments or exhibit an opposite trend favoring chemotherapy. This observation of context-dependent predictiveness remains strong regardless of immune subtype (Immune-Enriched or Non-Immune), PD-L1 regulation mechanism (adaptative or constitutive), tumor mutation burden, or neoantigen load. This work illuminates avenues for optimizing the use of PD-L1 expression in clinical decision-making and trial design, although this exploratory concept should be further confirmed in large trials.

Screen and Optimization of an Aptamer for Alexandrium tamarense-A Common Toxin-Producing Harmful Alga.

Among all the paralytic shellfish toxins (PSTs)-producing algae, Alexandrium tamarense is one of the most widespread harmful species posing a serious threat to marine resources and human health. Therefore, it is extremely important to establish a rapid and accurate monitoring method for A. tamarense that can provide early warnings of harmful algal blooms (HABs) caused by this alga and limit the contamination due to PSTs. In this study, an ssDNA library was first obtained by whole cell systematic evolution of ligands by exponential enrichment after 18 consecutive rounds of iterative screening. After sequencing in combination with subsequent multiple alignment of sequences and secondary structure simulation, the library could be classified into 2 families, namely, Family1 and Family2, according to sequence similarity. Flow cytometry was used to test the affinity and cross-reactivity of Ata19, Ata6, Ata25 and Ata29 belonging to Family2. Ata19 was selected to be modified by truncation, through which a new resultant aptamer named as Ata19-1-1 was obtained. Ata19-1-1 with a KD of 75.16 ± 11.10 nM displayed a much higher affinity than Ata19. The specificity test showed that Ata19-1-1 has the same discrimination ability as Ata19 and can at least distinguish the target microalga from other microalgae. The observation under a fluorescence microscopy showed that the A. tamarense cells labeled with Ata19-1-1 are exhibiting bright green fluorescence and could be easily identified, factually confirming the binding of the aptamer with target cells. In summary, the aptamer Ata19-1-1 produced in this study may serve as an ideal molecular recognition element for A. tamarense, which has the potential to be developed into a novel detection method for this harmful alga in the future.

Effectiveness of Tai Chi on cognitive function among older adults with mild cognitive impairment: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of Tai Chi on cognitive function in older adults with mild cognitive impairment. METHODS: A systematic search of eight English and five Chinese electronic databases was conducted to identify randomized controlled trials of Tai Chi as the intervention. The main outcomes included executive function, episodic memory, visuospatial function, working memory, concentration, memory complaints, and global cognition. The Cochrane RoB tool was used to assess bias in the study. Meta-analysis was conducted using Review Manager 5.4. Narrative syntheses were performed if meta-analysis was inappropriate. RESULTS: A total of eleven trials (905 participants) were included. Meta-analysis showed that Tai Chi significantly and moderately affected executive function (SMD = -1.01, 95% CI: -1.54 to -0.47, p < 0.001), episodic memory (SMD = 0.59, 95% CI: 0.24 to 0.94, p = 0.001), visuospatial function (SMD = 0.38, 95% CI: 0.15 to 0.60, p < 0.001), and global cognition (SMD = 0.57, 95% CI: 0.14 to 1.00, p = 0.01).One study showed that Tai Chi could improve verbal fluency. CONCLUSIONS: This review reveals that Tai Chi can improve executive function, episodic memory, visuospatial function, and global cognition in older adults with mild cognitive impairment, but not working memory, concentration, or memory complaints. These findings are consist with existing reviews about the effectiveness of Tai Chi. Long-duration (> 1500 min) Tai Chi is more effective for improving global cognition. However, the findings should be interpreted with caution due to the potential risk of bias and limited sample sizes of the included studies. Future trials should examine the effectiveness of standardized Tai Chi intervention on cognitive outcomes in older adults with mild cognitive impairment.

Association between negative parent-related family interactions and child social anxiety: A cross-cultural systematic review and meta-analysis.

This meta-analysis systematically evaluates the strength and direction of the association between negative parent-related family interactions and child social anxiety, and identifies several influencing moderators. Two investigators independently searched international (PsycINFO, PubMed, and Web of Science) and Chinese (CNKI, WanFang, and VIP) databases from their inception dates until March 5, 2023, for suitable articles. Of the 5771 identified records, 85 studies were selected based on inclusion of at least one of the following three dimensions of negative family interactions: insecure attachment (n = 27), parent-related family conflicts (n = 19), or negative parenting styles (n = 46). Meta-analyses showed that all three dimensions were significantly associated with child social anxiety (insecure attachment: r = 0.271, p < 0.0001; parent-related family conflicts: r = 0.226, p < 0.0001; negative parenting styles: r = 0.186, p < 0.0001). For all three dimensions, this association was stronger in children from East Asian culture than in those from European or American culture. In addition, age group, information source, and publication year also significantly moderated this association. Our findings will help guide further research and provide recommendations for the development of effective interventions for reducing social anxiety.

Characterization of CCoV-HuPn-2018 spike protein-mediated viral entry.

Canine coronavirus-human pneumonia-2018 (CCoV-HuPn-2018) was recently isolated from a child with pneumonia. This novel human pathogen resulted from cross-species transmission of a canine coronavirus. It has been known that CCoV-HuPn-2018 uses aminopeptidase N (APN) from canines, felines, and porcines, but not humans, as functional receptors for cell entry. The molecular mechanism of cell entry in CCoV-HuPn-2018 remains poorly understood. In this study, we demonstrated that among the nine APN orthologs tested, the APN of the Mexican free-tailed bat could also efficiently support CCoV-HuPn-2018 spike (S) protein-mediated entry, raising the possibility that bats may also be an alternative host epidemiologically important for the transmission of this virus. The glycosylation at residue N747 of canine APN is critical for its receptor activity. The gain of glycosylation at the corresponding residues in human and rabbit APNs converted them to functional receptors for CCoV-HuPn-2018. Interestingly, the CCoV-HuPn-2018 spike protein pseudotyped virus infected multiple human cancer cell lines in a human APN-independent manner, whereas sialic acid appeared to facilitate the entry of the pseudotyped virus into human cancer cells. Moreover, while host cell surface proteases trypsin and TMPRSS2 did not promote the entry of CCoV-HuPn-2018, endosomal proteases cathepsin L and B are required for the entry of CCoV-HuPn-2018 in a pH-dependent manner. IFITMs and LY6E are host restriction factors for the CCoV-HuPn-2018 entry. Our results thus suggest that CCoV-HuPn-2018 has not yet evolved to be an efficient human pathogen. Collectively, this study helps us understand the cell tropism, receptor usage, cross-species transmission, natural reservoir, and pathogenesis of this potential human coronavirus. IMPORTANCE Viral entry is driven by the interaction between the viral spike protein and its specific cellular receptor, which determines cell tropism and host range and is the major constraint to interspecies transmission of coronaviruses. Aminopeptidase N (APN; also called CD13) is a cellular receptor for HCoV-229E, the newly discovered canine coronavirus-human pneumonia-2018 (CCoV-HuPn-2018), and many other animal alphacoronaviruses. We examined the receptor activity of nine APN orthologs and found that CCoV-HuPn-2018 utilizes APN from a broad range of animal species, including bats but not humans, to enter host cells. To our surprise, we found that CCoV-HuPn-2018 spike protein pseudotyped viral particles successfully infected multiple human hepatoma-derived cell lines and a lung cancer cell line, which is independent of the expression of human APN. Our findings thus provide mechanistic insight into the natural hosts and interspecies transmission of CCoV-HuPn-2018-like coronaviruses.

Genomic Characteristics and Functional Analysis of Brucella sp. Strain WY7 Isolated from Antarctic Krill.

Antarctic krill (Euphausia superba) is a key species of the Antarctic ecosystem whose unique ecological status and great development potential have attracted extensive attention. However, the genomic characteristics and potential biological functions of the symbiotic microorganisms of Antarctic krill remain unknown. In this study, we cultured and identified a strain of Brucella sp. WY7 from Antarctic krill using whole-genome sequencing and assembly, functional annotation, and comparative genomics analysis. First, based on 16S rDNA sequence alignment and phylogenetic tree analysis, we identified strain WY7 as Brucella. The assembled genome of strain WY7 revealed that it has two chromosomes and a plasmid, with a total genome length of 4,698,850 bp and an average G + C content of 57.18%. The DNA-DNA hybridization value and average nucleotide identity value of strain WY7 and Brucella anthropi ATCC® 49188TM, a type strain isolated from human clinical specimens, were 94.8% and 99.07%, respectively, indicating that strain WY7 is closely related to Brucella anthropi. Genomic island prediction showed that the strain has 60 genomic islands, which may produce HigB and VapC toxins. AntiSMASH analysis results showed that strain WY7 might produce many secondary metabolites, such as terpenes, siderophores and ectoine. Moreover, the genome contains genes involved in the degradation of aromatic compounds, suggesting that strain WY7 can use aromatic compounds in its metabolism. Our work will help to understand the genomic characteristics and metabolic potential of bacterial strains isolated from Antarctic krill, thereby revealing their roles in Antarctic krill and marine ecosystems.

Non-suicidal self-injury in Chinese population: a scoping review of prevalence, method, risk factors and preventive interventions.

Non-suicidal self-injury behavior (NSSI) is a serious public health concern that requires immediate attention. Despite the high prevalence of NSSI among the Chinese population, there is a significant gap in research on the comprehensive picture of this field. Therefore, a scoping review was conducted to investigate the prevalence, methods, risk factors, and preventive intervention programs related to NSSI in China. The review found that the estimated lifetime prevalence of NSSI among Chinese youth population is alarmingly high at 24.7% (N = 1,088,433). Common methods of NSSI include scratching, hitting, and biting. Additionally, the review synthesized 249 risk factors based on the biopsychosocial-ecological framework, highlighting the urgent need for intervention. However, only 12 empirical studies focus on NSSI prevention or intervention programs were included. These findings underscore the necessity for more clinical practices and larger studies to identify effective interventions and ultimately alleviate the burden of NSSI on the Chinese population. Funding: This review was supported by Humanity and Social Science Youth foundation of Ministry of Education (22YJCZH018), Science and Technology Innovation 2030 (STI2030-Major Projects:2021ZD0200702), National Natural Science Foundation of China (81825009), and Shuimu Tsinghua Scholar. No funding agencies were involved in the data collection, data analysis, and writing of this paper.

ZNF500 abolishes breast cancer proliferation and sensitizes chemotherapy by stabilizing P53 via competing with MDM2.

Zinc finger protein 500 (ZNF500) has an unknown expression pattern and biological function in human tissues. Our study revealed that the ZNF500 mRNA and protein levels were higher in breast cancer tissues than those in their normal counterparts. However, ZNF500 expression was negatively correlated with advanced TNM stage (p = 0.018), positive lymph node metastasis (p = 0.014), and a poor prognosis (p < 0.001). ZNF500 overexpression abolished in vivo and in vitro breast cancer cell proliferation by activating the p53-p21-E2F4 signaling axis and directly interacting with p53 via its C2H2 domain. This may prevent ubiquitination of p53 in a manner that is competitive to MDM2, thus stabilizing p53. When ZNF500-∆C2H2 was overexpressed, the suppressed proliferation of breast cancer cells was neutralized in vitro and in vivo. In human breast cancer tissues, ZNF500 expression was positively correlated with p53 (p = 0.022) and E2F4 (p = 0.004) expression. ZNF500 expression was significantly lower in patients with Miller/Payne Grade 1-2 than in those with Miller/Payne Grade 3-5 (p = 0.012). ZNF500 suppresses breast cancer cell proliferation and sensitizes cells to chemotherapy.

Nanofiber-Reinforced Composite Gel Enabling High Ionic Conductivity and Ultralong Cycle Life for Zn Ion Batteries.

Despite the impressive merits of gel electrolytes for aqueous Zn-ion batteries, it remains a significant challenge to design and develop the gel electrolyte with high ionic conductivity, excellent dimensional stability, and long cycle life. Herein, a composite electrolyte (PTP) with thermolastic polyurethane -poly(m-phenylene isophthalamide)  nanofiber-reinforced polyvinyl alcohol gel strategy is proposed for highly reversible Zn plating/stripping. Mechanically robust and ultrathin PTP contains functional groups for building ion migration channels and immobilizing water molecules, which accelerates Zn2+ migration and mitigates water-related side reactions. Thus, the Zn anodes exhibit excellent electrochemical performance involving high cycling stability (6500 h at 5 mA cm-2 , 5 mA h cm-2 ) and achieving an exceptional cumulative capacity of more than 16 000 mA h cm-2 . This enhancement is well maintained when combined with MnO2 cathode. This work provides a reasonable solution for stabilizing Zn anodes and also provides new ideas for the modification of nanofiber-reinforced gel electrolytes.

Anxiety and Depression Symptoms among Youth Survivors of Childhood Sexual Abuse: A Network Analysis.

BACKGROUND: Previous studies have frequently reported a high prevalence of co-occurring anxiety and depression among people who experienced stressful events in childhood. However, few have noted the symptomatic relationship of this comorbidity among childhood sexual abuse (CSA) survivors. Therefore, this study's objectives were as follows: (1) to examine the relationship across symptoms between anxiety and depression among CSA survivors; (2) to compare differences between male and female network structures among CSA survivors. METHODS: A total of 63 Universities and Colleges in Jilin Province, China, covered 96,218 participants in this study, a sub-set data of which met the criteria of CSA was analyzed with the network analysis. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), measured CSA. Anxiety was measured by the seven-item Generalized Anxiety Disorder Scale (GAD-7), and depression was measured by the Patient Health Questionnaire (PHQ-9). The sex difference between anxiety and depression among CSA survivors was compared. RESULTS: 3,479 college students reported the experience of CSA (CTQ-SF total scores ≥ 8), with a prevalence of 3.62% (95% CI: 3.50-3.73%). Among CSA survivors, control worry, sad mood, and energy were central and bridge symptoms of the anxiety and depression network. Meanwhile, male CSA survivors appeared to have a stronger correlation between guilt and suicide, but female CSA survivors seemed to have a stronger correlation between control worry and suicide. Moreover, the edge of control worry-relax-afraid was stronger in the male network, while the edge of restless-relax was stronger in the female network. CONCLUSION: Control worry, sad mood, and energy are crucial to offer targeted treatment and to relieve anxiety and depression symptoms for CSA survivors. Guilt needs more attention for male CSA survivors, while control worry remains more important for female CSA survivors to reduce suicidal ideation and suicide attempts.

The construction of a biomass component interaction model based on research into the hydrothermal liquefaction of sewage sludge.

Sewage sludge (SS), a hazardous solid waste with a high water and pollutant content, should be disposed of correctly. Hydrothermal liquefaction (HTL) shows tremendous potential to treat organic matter with substantial water content like SS. In this paper, we examined the impact of key factors on the characteristics and yield of bio-oil during HTL of SS. We clarified the impacts of each component on the yield through model compounds based on that and constructed a component additivity model for forecasting the bio-oil yield from biomass with complex component composition. In the reactions of the model compounds, cellulose showed synergistic interaction with protein and alkali lignin in the bio-oil yield but lipids showed antagonistic effects with protein and alkaline lignin. The co-HTL results of these binary mixtures improved our model and further clarified the reaction mechanism of HTL of SS.

Silk Nanofiber Scaffolds with Multiple Angiogenic Cues to Accelerate Wound Regeneration.

Niches with multiple physical and chemical cues can influence the fate of cells and tissues in vivo. Simulating the in vivo niche in the design of bioactive materials is a challenge, particularly to tune multiple cues simultaneously in the same system. Here, an assembly strategy was developed to regulate multiple cues in the same scaffold based on the use of two silk nanofiber components that respond differently during the fabrication processes. An aqueous solution containing the two components, amorphous silk nanofibers (ASNFs) and ß-sheet-rich silk nanofibers (BSNFs), was sequentially treated with an electrical field and freeze-drying processes where the BSNFs oriented to the electrical field, while the ASNFs formed stable porous structures during the lyophilization process to impact the mechanical properties. Bioactive cargo, such as deferoxamine (DFO), was loaded on the BSNFs to enrich cell responses with the scaffolds. The in vitro results revealed that the loaded DFO and the anisotropic structures with improved mechanical properties resulted in better vascularization than those of the scaffolds without the anisotropic features. The multiple cues in the scaffolds provided angiogenic niches to accelerate wound healing.

Ultrasound Molecular Imaging of Bladder Cancer via Extradomain B Fibronectin-Targeted Biosynthetic GVs.

Purpose: Ultrasound molecular imaging (UMI) has proven promising to diagnose the onset and progression of diseases such as angiogenesis, inflammation, and thrombosis. However, microbubble-based acoustic probes are confined to intravascular targets due to their relatively large particle size, greatly reducing the application value of UMI, especially for extravascular targets. Extradomain B fibronectin (ED-B FN) is an important glycoprotein associated with tumor genesis and development and highly expressed in many types of tumors. Here, we developed a gas vesicles (GVs)-based nanoscale acoustic probe (ZD2-GVs) through conjugating ZD2 peptides which can specially target to ED-B FN to the biosynthetic GVs. Materials and Methods: ED-B FN expression was evaluated in normal liver and tumor tissues with immunofluorescence and Western blot. ZD2-GVs were prepared by conjugating ZD2 to the surface of GVs by amide reaction. The inverted microscope was used to analyze the targeted binding capacity of ZD2-GVs to MB49 cells (bladder cancer cell line). The contrast-enhanced imaging features of GVs, non-targeted control GVs (CTR-GVs), and targeted GVs (ZD2-GVs) were compared in three MB49 tumor mice. The penetration ability of ZD2-GVs in tumor tissues was assessed by fluorescence immunohistochemistry. The biosafety of GVs was evaluated by CCK8, blood biochemistry, and HE staining. Results: Strong ED-B FN expression was observed in tumor tissues while little expression in normal liver tissues. The resulting ZD2-GVs had only 267.73 ± 2.86 nm particle size and exhibited excellent binding capability to the MB49 tumor cells. The in vivo UMI experiments showed that ZD2-GVs produced stronger and longer retention in the BC tumors than that of the non-targeted CTR-GVs and GVs. Fluorescence immunohistochemistry confirmed that ZD2-GVs could penetrate the tumor vascular into the interstitial space of the tumors. Biosafety analysis revealed there was no significant cytotoxicity to these tested mice. Conclusion: Thus, ZD2-GVs can function as a potential UMI probe for the early diagnosis of bladder cancer.

Biplanar Acromioplasty: An Arthroscopic Spur Removal Technique Based on Original Bony Landmarks.

In this study, we introduce an arthroscopic acromioplasty technique based on original bony landmarks, namely biplanar acromioplasty. This technique focuses on smoothing both the coronal and transverse plane of acromion, corresponding to the anterior and inferior acromial surface, and restores the acromion to its original shape. We believe this technique is effective, time-saving, and reproducible.

Genetic dissection of lint percentage in short-season cotton using combined QTL mapping and RNA-seq.

KEY MESSAGE: In total, 17 QTLs for lint percentage in short-season cotton, including three stable QTLs, were detected. Twenty-eight differentially expressed genes located within the stable QTLs were identified, and two genes were validated by qRT-PCR. The breeding and use of short-season cotton have significant values in addressing the question of occupying farmlands with either cotton or cereals. However, the fiber yields of short-season cotton varieties are significantly lower than those of middle- and late-maturing varieties. How to effectively improve the fiber yield of short-season cotton has become a focus of cotton research. Here, a high-density genetic map was constructed using genome resequencing and an RIL population generated from the hybridization of two short-season cotton accessions, Dong3 and Dong4. The map contained 4960 bin markers across the 26 cotton chromosomes and spanned 3971.08 cM, with an average distance of 0.80 cM between adjacent markers. Based on the genetic map, quantitative trait locus (QTL) mapping for lint percentage (LP, %), an important yield component trait, was performed. In total, 17 QTLs for LP, including three stable QTLs, qLP-A02, qLP-D04, and qLP-D12, were detected. Three out of 11 non-redundant QTLs overlapped with previously reported QTLs, whereas the other eight were novel QTLs. A total of 28 differentially expressed genes associated with the three stable QTLs were identified using RNA-seq of ovules and fibers at different seed developmental stages from the parental materials. The two genes, Ghir_A02G017640 and Ghir_A02G018500, may be related to LP as determined by further qRT-PCR validation. This study provides useful information for the genetic dissection of LP and promotes the molecular breeding of short-season cotton.

Accelerating Wound Closure with Metrnl in Normal and Diabetic Mouse Skin.

Impaired wound healing and ulcer complications are major causes of morbidity in patients with diabetes. Impaired wound healing is associated with increased inflammation and poor angiogenesis in diabetes patients. Here, we demonstrate that topical administration of a secreted recombinant protein (Meteorin-like, Metrnl) accelerates wound epithelialization and angiogenesis in mice. We observed a significant increase in Metrnl expression during physiological wound healing; however, its expression remained low during diabetic wound healing. Functionally, the recombinant protein Metrnl significantly accelerated wound closure in normal and diabetic mice models including db/db, high-fat diet/streptozotocin (HFD/STZ), and STZ mice. Mechanistically, keratinocytes secrete quantities of Metrnl to promote angiogenesis, increase endothelial cell proliferation, migration and tube formation, and enhance macrophage polarization to the M2 type. Meanwhile, M2 macrophages secrete Metrnl to further stimulate angiogenesis. Moreover, the keratinocyte- and macrophage-produced cytokine Metrnl drives post-injury angiogenesis and re-epithelialization through activation of AKT phosphorylation (S473) in a KIT receptor tyrosine kinase (c-Kit)-dependent manner. In conclusion, our study suggests that Metrnl has a biological activity in accelerating wound closure through c-Kit-dependent angiogenesis and epithelialization.