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Xiangnan Qiu,1 Changchen Jiang,1 Shenghua Jing,1 Aomei Li,1 Xiangdong Sun,1 Zetian Shen2 1Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China; 2Department of Radiation Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210031, People’s Republic of ChinaCorrespondence: Zetian Shen; Xiangdong Sun, Email sztflk@163.com; sxdflk@163.comPurpose: The standard treatment regimen of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is still controversial. The purpose of this study was to analyze the efficacy and safety of preoperative intensive CRT in our institution.Methods: A retrospective data collection and analysis of 181 LARC patients receiving oxaliplatin (85%) of standard doses in capecitabine-based preoperative CRT and two additional cycle of neoadjuvant chemotherapy between the end of concurrent CRT and surgery.Results: The compliance of the preoperative CRT was satisfactory with 99.4%patients completed radiotherapy and 97.19%patients completed all 2 cycles of concurrent chemotherapy. Except for 20 patients diagnosed clinical complete remission (cCR) managed according to watch and wait strategy, 160 patients received R0 radical surgery. The pathological complete response (pCR) rate was 23.75% (38/160) and tumor regression grade (TRG) 0/1 was 40% (72/180). In terms of tumor downstaging, 89 (55.63%) had T downstaging while 115 (71.88%) had N downstaging. The 1-overall survival (OS),2-OS,3-OS and 5-OS were 98.7%, 96.5%, 91.4% and 81.5%, respectively. The total rate of sphincter preservation was 86.25% (138/160) and the rate of patients with low rectal cancer was 73.0% (54/74) without affecting local control rates and survival rates. Both acute adverse reactions to preoperative CRT and postoperative complications were tolerable and controllable.Conclusion: In this retrospective study, preoperative intensive CRT of patients with LARC achieved satisfied disease control and survival outcomes and well acquired the sphincter retention rate in recent years in our institution. On the basis of these findings, a Phase III study to definitively test the intensified preoperative CRT strategy is warranted.Keywords: rectal cancer, preoperative chemoradiotherapy, overall survival, disease control

Shengyu Jing,1,2 Hongjie Li,1,2 Hongbo Xu1 1Department of Vascular Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hongbo Xu, Department of Vascular Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 13973112593, Fax +86 73188618034, Email xu.hongbo@csu.edu.cnAbstract: Nowadays, refractory diabetic wounds cause a worldwide medical burden. Mesenchymal stem cells derived exosomes (MSC-Exos) show promise as a solid alternative to existing therapeutics in the latest researches, since MSC-Exos share similar biologic activity but less immunogenicity when compared with MSCs. To facilitate further understanding and application, it is essential to summarize the current progress and limitations of MSC-Exos in the treatment of diabetic wounds. In this review, we introduce the effects of different MSC-Exos on diabetic wounds according to their origins and contents and discuss the specific experimental conditions, target wound cells/pathways, and specific mechanisms. In addition, this paper focuses on the combination of MSC-Exos and biomaterials, which improves the efficacy and utilization of MSC-Exos therapy. Together, exosome therapy has high clinical value and application prospects, both in its role and in combination with biomaterials, while novel drugs or molecules loaded into exosomes as carriers targeting wound cells will be development trends.Keywords: diabetic wound, mesenchymal stem cell, exosome, biomaterial

Shangwen Jing,1,* Yantong Lu,1,2,* Jing Zhang,1 Yan Ren,1,2 Yousheng Mo,3 Dongdong Liu,3 Lining Duan,4 Zhongyu Yuan,5 Changjun Wang,2 Qi Wang1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, People’s Republic of China; 3The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Medical Oncology, Sun Yat-Sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changjun Wang; Qi Wang, Email gzwchj@126.com; wangqi@gzucm.edu.cnIntroduction: Breast cancer (BC) is the leading female malignancy, with one million new cases diagnosed worldwide per year. However, the current treatment options for BC patients have difficulty achieving satisfactory efficacy. Ferroptosis is a new mode of regulated cell death that plays a key role in the inhibition of tumorigenesis. Levistilide A (LA), as an active compound extracted from Chuanxiong Rhizoma, might prevent the development of tumors by regulating the critical cellular processes of ferroptosis.Methods: In this study, the underlying mechanisms of LA on ferroptosis in BC were explored in vitro. The effect of LA on the viability and mitochondrial function of BC cells was determined. Moreover, the effect of LA on the expression levels of key molecules involved in ferroptosis and the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway was evaluated.Results: LA significantly reduced cell viability and damaged the mitochondrial structure and function of BC cells in a dose-dependent manner. Furthermore, LA treatment markedly enhanced reactive oxygen species (ROS)-induced ferroptosis by activating the Nrf2/HO-1 signaling pathway.Conclusion: These findings suggest that LA may be a potential lead compound for breast cancer therapy by inducing ferroptosis in tumor cells.Keywords: breast cancer, levistilide A, ferroptosis, Nrf2/HO-1 signaling pathway

Siqun Jing,1 Zhengmei Zhao,2 Jinzi Wu,3 Liang-Jun Yan3 1Yingdong Food College, Shaoguan Unversity, Shaoguan, Guangdong 512005, People’s Republic of China; 2College of Life Sciences and Technology, Xinjiang University, Urumqi, Xinjiang 830046, People’s Republic of China; 3Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USACorrespondence: Siqun Jing; Liang-Jun Yan Tel/ Fax +86-0751-8120167; Tel +1 817-735-2386; Fax +1 817-735-2603Email jingsiqun@163.com; liang-jun.yan@unthsc.eduIntroduction: The purpose of the present study was to reveal the potential positive effect of the Ta-ermi extracts on oxidative stress and streptozotocin (STZ)-diabetic mice and rats treated with Ta-ermi water- and alcohol-extracts.Methods: The study was carried out using three experimental model: 1) in vitro experiments whereby Ta-ermi extracts were incubated with free radical generators such as 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) to evaluate Ta-ermi’s antioxidant effects; 2) testing the hypoglycemic effects of Ta-ermi extracts in streptozotocin (STZ)-induced diabetic mice; and 3) testing the beneficial effects of Ta-ermi extracts on mitochondrial complex I function using STZ-diabetic rats.Results: In vitro antioxidant experiments showed that both of the extracts could scavenge free radicals and exhibited inhibitory effects on glucosidase and aldose reductase with differential effects between water extract and alcohol extract. In the STZ mouse diabetic model, both the water- and alcohol-extracts attenuated body weight decrease, decreased blood glucose levels in a concentration-dependent manner, improved insulin sensitivity, and increased oral glucose tolerance ability. In the STZ-diabetic rat model, both the water- and alcohol-extracts were found to be able to lower blood glucose levels in the diabetic animals with no effects on body weight changes. Moreover, in the STZ-diabetic rats, both the water- and alcohol-extracts of Ta-ermi could inhibit the increase of mitochondrial NADH/ubiquinone oxidoreductase (complex I) activity in the pancreas and enhanced complex I activity in the liver but showed no effect on lung or kidney mitochondrial complex I.Discussion: The present study points to the potential medicinal value of Ta-ermi’s water and alcohol extracts in lowering blood glucose and decreasing diabetic oxidative stress. One limitation of our study is that the compound or compounds that actually have this beneficial effect in the extracts remain unknown at this time. Therefore, the future studies should be focused on the identification of the components in the extracts that exhibit anti-oxidative and hypoglycemic effects.Conclusion: Taken together, our studies using different experimental paradigms indicate that Ta-ermi extracts possess antioxidant and anti-diabetic properties and may be employed as functional food ingredients for the remission of diabetes.Keywords: Ta-ermi extracts, antioxidant activity, anti-diabetic, mitochondrial complex I, streptozotocin

Guiying Yang, Xiaohang Bao, Jing Peng, Jie Li, Guangming Yan, Sheng Jing, Hong Li, Guangyou Duan Department of Anesthesiology, Second Affiliated Hospital of Army Medical University, Chongqing 400037, People’s Republic of ChinaCorrespondence: Hong Li; Guangyou DuanDepartment of Anesthesiology, Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of ChinaTel +8618323376014Fax +862368774997Email lh78553@163.com; dgy1986anesthesia@126.comPurpose: This study aimed to compare the analgesic outcomes between primary and repeated cesarean delivery.Patients and Methods: We performed a retrospective analysis based on the medical records of a teaching hospital in China from January 2018 to March 2019. We collected data on demographic characteristics, perioperative complications, anesthesia, and surgical factors for cesarean delivery patients. We also recorded the postoperative analgesic strategy, pain intensity (assessed by the number rating scale) during the first 48 hrs after surgery, hospital cost, and hospital stay. Postoperative inadequate analgesia was defined by a score of ≥ 4 in the number rating scale. Analgesic outcomes after cesarean delivery between primiparas and multiparas were compared using propensity score matching analysis. Moreover, subgroup logistic analysis for different age groups (≥ 35 and < 35 years) was performed to investigate the effect of the maternal category on postoperative inadequate analgesia.Results: A total of 1543 patients were included in the analysis and 571 pairs (1142 patients) were matched in the primiparas and multiparaparas group according to their propensity score. In both the non-matched and matched cohort, the incidence of inadequate analgesia in the primiparas group was lower than that in the multiparas group (16.7% vs. 24.0%, P < 0.001 and 16.1% vs. 23.5%, P = 0.002; respectively). The multiparas group was identified as being at risk of inadequate analgesia after cesarean delivery in both age groups (age ≥ 35 years, odds ratio: 2.18, 95% confidence interval: 1.20– 3.95; age < 35 years, odds ratio: 1.43, 95% confidence interval 1.08– 1.89).Conclusion: Multiparas that undergo a repeat cesarean delivery had a significantly higher risk of inadequate postoperative pain treatment than primiparas. The maternal category should be considered when formulating the postoperative analgesia strategy after cesarean delivery.Keywords: cesarean delivery, analgesia, primipara, multipara

Xin Li,1 Jiaqi Gao,1 Zepeng Yu,1 Weihai Jiang,2 Wei Sun,2 Chunyan Yu,1 Jinghui Sun,1 Chunmei Wang,1 Jianguang Chen,1 Shu Jing,2 He Li1 1Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, Jilin 132013, People’s Republic of China; 2Affiliated Hospital of Beihua University, Jilin, Jilin 132011, People’s Republic of ChinaCorrespondence: Shu Jing; He Li Email yitongjingshu@163.com; yitonglh@126.comBackground: Aging is a spontaneous and inevitable phenomenon of biology, which can lead to the gradual deterioration of tissues and organs. One of the age-related deterioration processes is immunosenescence, which leads to changes in the function of immune systems, including immune cells and associated cytokines. A proper modulation of immune responses can improve the age-related immunosenescence process and then reach healthy aging. Schisandra sphenanthera, a traditional Chinese medicine, has been used as both a medicine and a nutritional supplement for thousands of years. Anwulignan, a monomer compound of Schisandra sphenanthera lignans, has been reported to possess an immunomodulatory effect. Therefore, this study was designed to further explore whether Anwulignan could also modulate the immune functions in aging model mice and the underlying mechanism.Methods: D-galactose (D-gal) is often used as an inducer of immunosenescence in animals. In this study, a mice model was created by subcutaneous D-gal (220 mg kg− 1) for successive 42 days. Then, the blood and spleen tissue samples were taken for the analysis and observation of cytokine levels, immunoglobulin levels, leukocyte numbers, and the phagocytic activity of macrophages, as well as the histological changes, the proliferation ability of lymphocytes, and the biochemical parameters in the spleen tissue.Results: Anwulignan significantly increased the serum levels of IL-2, IL-4, IFN-γ, lgG, lgM, and lgA, decreased the content of TNF-α and IL-6 in the aging mice, and increased the blood leukocyte number, the phagocytic activity, the lymphocyte proliferation, and the spleen index in vitro. Anwulignan also significantly increased the activities of SOD and GSH-Px, decreased the contents of MDA and 8-OHdG in the spleen tissue, up-regulated the expressions of Nrf2, HO-1, and Bcl2, down-regulated the expressions of Keap1, Caspase-3, and Bax in the spleen cells, and reduced the apoptosis of spleen lymphocytes.Conclusion: Anwulignan can restore the immune function that is declined in D-gal-induced aging mice partly related to its antioxidant capacity by activating the Nrf2/ARE pathway and downstream enzymes, as well as its anti-apoptotic effect by regulating Caspase-3 and the ratio of Bcl2 to Bax in the spleen.Keywords: Anwulignan, immunosenescence, antioxidation, anti-apoptosis

Jiaqi Gao,1,* Zepeng Yu,1,* Shu Jing,2 Weihai Jiang,2 Cong Liu,1 Chunyan Yu,1 Jinghui Sun,1 Chunmei Wang,1 Jianguang Chen,1 He Li1 1Department of Pharmacology, College of Pharmacy, Beihua University, Jilin City, People’s Republic of China; 2Affiliated Hospital of Beihua University, Jilin City, People’s Republic of China *These authors contributed equally to this work Background: Liver aging is a significant risk factor for chronic liver diseases. Oxidative stress has been considered as a conjoint pathological mechanism for the initiation and progression of liver aging. It has been reported that D-galactose (D-gal)-induced hepatic injury is an experimental model well established closely similar to morphological and functional features of liver aging. Schisandra sphenanthera Rehd. et Wils (S. sphenanthera, Schisandraceae), as a famous tradi-tional Chinese medicine, has been used for thousands of years in China to treat various disorders, including liver dysfunctions. This study was aimed to understand whether Anwulignan, one of the monomeric compounds in the lignans from S. sphenanthera, could improve the hepatic injury induced by D-gal in mice and to examine the possible mechanisms. Methods: ICR mice were used to produce hepatic injury by 220 mg kg-1 D-gal subcutaneously once daily for 42 days. The effects of oral Anwulignan on liver index; serial AST and ALT levels; histological changes; SOD, GSH-Px, MDA, and 8-OHdG in the liver and peripheral blood; expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver; and HepG2 cell viability, and decrease caspase-3 contents in liver were examined. Results: Anwulignan could significantly increase the liver index, lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the peripheral blood, elevate superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decrease malonaldehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) contents in the peripheral blood and liver. Furthermore, Anwulignan could upregulate the expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver, increase the HepG2 cell viability, and decrease caspase-3 contents in liver. Conclusion: Anwulignan has protective effects against the hepatic injury induced by D-gal, which may be related to its antioxidant capacity through activating p38 MAPK–Nrf2–HO-1 pathway, increases the injured cell viability, and decreases the caspase-3 contents in liver. Keywords: Schisandra, antioxidant capacity, caspase-3

Jinghui Sun,1 Shu Jing,2 Rui Jiang,3 Chunmei Wang,1 Chengyi Zhang,1 Jianguang Chen,1 He Li1 1Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, People’s Republic of China; 2General Surgery Area, Affiliated Hospital of Beihua University, Jilin, People’s Republic of China; 3Jilin Technology Innovation Center for Chinese Medicine Biotechnology, College of Chemistry and Biology, Beihua University, Jilin, People’s Republic of China Objective: The aim of this study was to evaluate the antiaging effect of Schisandra chinensis lignans (SCL) by analyzing the characteristics in the serum of d-galactose (d-gal)-induced rats.Methods: Forty male Wistar rats were randomly divided into control group, d-gal model group, low-dose SCL group (50 mg/kg/d), medium-dose SCL group (100 mg/kg/d), and high-dose SCL group (200 mg/kg/d). A serum metabolomics analysis method based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry was carried out to study the characteristics of d-gal-induced aging rats and evaluate the antiaging effects of SCL, and multivariate statistical analysis was performed for pattern recognition and characteristic metabolites identification. The relative levels of p19, p53, and p21 genes in the brain tissue were measured by quantitative real-time polymerase chain reaction for investigating the underlying mechanism. Results: Metabolomics analysis showed that 15 biomarkers were identified and 13 of them recovered to the normal levels after the administration of SCL. Based on the pathway analysis, the antiaging mechanisms of SCL might be involved in the following metabolic pathways: energy, amino acid, lipid, and phospholipid metabolism. Furthermore, SCL significantly inhibited the mRNA expression level of p19, p53, and p21 in the brain of aging rats induced by d-gal. Conclusion: These results suggest that SCL can delay rat aging induced by d-gal through multiple pathways. Keywords: Schisandra chinensis lignans, aging, rat, metabolomics, RRLC-Q-TOF-MS, RT-PCR

Adopting a systems approach, we devise a general workflow to define actionable subtypes in human cancers. Applied to small cell lung cancer (SCLC), the workflow identifies four subtypes based on global gene expression patterns and ontologies. Three correspond to known subtypes (SCLC-A, SCLC-N, and SCLC-Y), while the fourth is a previously undescribed ASCL1+ neuroendocrine variant (NEv2, or SCLC-A2). Tumor deconvolution with subtype gene signatures shows that all of the subtypes are detectable in varying proportions in human and mouse tumors. To understand how multiple stable subtypes can arise within a tumor, we infer a network of transcription factors and develop BooleaBayes, a minimally-constrained Boolean rule-fitting approach. In silico perturbations of the network identify master regulators and destabilizers of its attractors. Specific to NEv2, BooleaBayes predicts ELF3 and NR0B1 as master regulators of the subtype, and TCF3 as a master destabilizer. Since the four subtypes exhibit differential drug sensitivity, with NEv2 consistently least sensitive, these findings may lead to actionable therapeutic strategies that consider SCLC intratumoral heterogeneity. Our systems-level approach should generalize to other cancer types.

Living closely with others can provide a myriad of fitness benefits, from shared territory defense to co-operative resource acquisition. Costs of social aggregation are not absent, however, and likely influence optimal and observed groups' sizes in a social species. Here, we explored optimal group size in a joint-nesting cuckoo species (the Smooth-billed Ani, Crotophaga ani) using endocrine markers of stress physiology (corticosterone, or CORT). Smooth-billed Anis exhibit intense reproductive competition that is exacerbated in atypically large groups. We therefore hypothesized that intra-group competition (measured by social group size) mediates the desirability and physiological cost of social group membership in this species. To test this hypothesis, we captured 47 adult Smooth-billed Anis (31 males, 16 females) during the breeding seasons of 2012-2014 in south-western Puerto Rico, and documented social group sizes. Tail feathers were sampled and used to quantify CORT (pg/mg) in enzyme-linked immunosorbent assays (ELISAs) (n = 50). Our analyses show significant differences in feather-CORT of adults between categorical group sizes, with individuals from atypically large social groups (≥ x + 1SD) having highest mean concentrations (33.319 pg/mg), and individuals from atypically small social groups (≤ x - 1SD) having lowest mean concentrations (8.969 pg/mg). Whether reproductive competition or effort is responsible for elevated CORT in atypically large social groups, however, remains unclear. Our results suggest that living in atypically large groups is physiologically expensive and may represent an evolutionarily unstable strategy. To our knowledge, this is the first study to explore a correlation between stress physiology and group size in a joint-nesting species.

The effect of hostage, the instar of Bemisia tabaci (Gennadius) parasitized, on the growth and development of Encarsia formosa (Gahan) was studied. E. formosa was able to parasitize and complete its life cycle no matter which instar of B. tabaci (Strain B), [also identified as B. argentifolii (Bellows and Perring)], was provided for oviposition, but parasitoid development was significantly slower when 1st or 2nd instar B. tabaci rather than 3rd or 4th instars were parasitized. Host age influenced the day on which E. formosa nymphs hatching from eggs was first observed. Mean embryonic development was significantly longer when 1st (5.4 days) rather than 2nd, 3rd or 4th instars (4.1, 3.4 and 3.5 days, respectively) were parasitized. The duration of the 1st instar parasitoid and the pupa, but not the 2nd or 3rd instar parasitoid, were also significantly greater when 1st instars were parasitized than when older host instars were parasitized. Interestingly, no matter which instar was parasitized, the parasitoid did not molt to the 3rd instar until the 4th instar host had reached a depth of about 0.23 mm (Stage 4-5) and had initiated the nymphal-adult molt and adult development. Histological studies revealed that whitefly eye and wing structures had either disintegrated or were adult in nature whenever a 3rd instar parasitoid was present. It appears, then, that the molt of the parasitoid to its last instar is associated with the host whitefly's nymphal-adult molt. However, the initiation of the host's final molt, while a prerequisite for the parasitoid's 2nd-3rd instar molt, did not necessarily trigger this molt. In contrast to its significant effect on various aspects of parasitoid development, host instar did not significantly influence the mean size of the parasitoid larva, pupa, or adult. Larval and pupal length and adult head width were similar for all parasitoids, regardless of which host instar was parasitized as was adult longevity. Adult parasitoid emergence was more synchronous when 2nd, 3rd and 4th instars were parasitized than when 1st instars were parasitized. Results are compared with those reported when the greenhouse whitefly, Trialeurodes vaporariorum, was parasitized by E. formosa, and provide possible explanations for why T. vaporariorum is a more suitable host than B. tabaci for E. formosa.

Colorado potato beetles have been reared successfully through 12 generations on artificial diets containing either 2.5% potato leaf powder or 2.5% lettuce leaf powder/0.75% potato leaf powder. For all but one of the treatment groups, the mean duration of each of the four larval stages was between 0.8 and 1.5 days longer than the durations exhibited by control beetles that had been fed on potato leaves. Maximum weights of prepupae, newly emerged adults and day 5 - 9 adults were approximately 78, 80 and 82%, respectively, of the weights for comparable stages of control beetles. Mean percent mortality for 1st instars was two to six times higher for artificial diet-fed CPBs than for leaf-fed beetles. However, since pupal mortality was four times higher for control beetles than for beetles reared on artificial diet, mean percent total mortality (newly hatched through the 9 day old adult) was equivalent for leaf-fed beetles and for later generations of potato and Lettuce+Potato diet-fed CPBs. Hemolymph ecdysteroid levels and fluctuations in mature 4th instar larvae and prepupae were similar in controls and experimental groups. Number of hatchlings produced per adult pair per day (fertility) was approximately eight times greater in control beetles than in later generations of artificial diet-fed beetles, primarily because fewer egg masses were laid per day, percent hatch was lower and cannibalism of eggs was higher in these latter groups. Interestingly, the mean percent hatch, although only 68% of the control value, was 1.5 times greater for beetles reared on diet containing lettuce-leaf powder, and a small percentage of potato leaf powder, than on diet containing only potato leaf powder. Percent hatch was equal for beetles fed on diet containing only lettuce-leaf powder and those fed on potato leaves.

World authorities and educators have taken attention to the issue of student dropout rates, which is a global concern. The rising dropout rates at all educational levels are mostly caused by financial difficulty. Consequently, Morong National High School confronts the same challenge. Because of this, the researchers look into the rates of dropouts from Morong National High School as well as the causes behind them in order to identify patterns and propose strategies to lower the dropout rate. A qualitative method was used in this study. The dropout rate was analyzed, four Grade Level Coordinators (GLCs), one LIS, and selected teachers participated in interview sessions regarding the reasons and their suggestions for all dropout students. The findings showed that Morong National High School (MNHS) has a varied dropout rate in each timeline (pre-pandemic, during pandemic and post-pandemic). The study found that pre-pandemic has the most drop out rate while the post-pandemic has the least student drop out rate. Based on the study, implementing particular guidelines into place may help decrease Morong National High School's dropout rate. Grade level advisers suggest offering financial aid to students and holding quarterly parent and student orientations. It is suggested that the school keep offering programs and solutions to deal with these issues, alongside encouraging teacher collaboration with parents to motivate students to attend courses. [ABSTRACT FROM AUTHOR]

Abstract Background In recent years, the use of endocrine-disrupting chemicals (EDCs) has become increasingly common, leading to severe environmental pollution and harm to aquatic organisms. 17α-Methyltestosterone (MT) is a synthetic androgen that can cause immunotoxicity in aquaculture, affecting fish health. To address this issue, this study aimed to investigate the effect of Vitamin C (VC) on MT-induced immunotoxicity and determine the optimal VC supplementation. Results Carassius auratus was exposed to 50 ng/L MT and treated with 25, 50, and 150 mg/kg VC for 7, 14, and 21 d. Morphological indicators, histological characteristics, hepatic antioxidant capacity, and immune-related gene expression were analyzed. Additionally, RNA-seq was performed on the liver tissues of the control, MT, and MT + 25 mg/kg VC groups after 21 d. Results showed that, MT treatment significantly increased liver malondialdehyde content and inhibited immune-related gene expression (TNF-α, IL-8, INF-γ, IL-10, Caspase-9, and IGF-I), causing oxidative stress and immunotoxicity, leading to hepatic steatosis. However, supplementation with 25–50 mg/kg VC effectively alleviated the MT-induced damage to the hepatic structure and immune system. RNA-seq revealed significant enrichment of differentially expressed genes in multiple signaling pathways, including the mTOR, MAPK, and Wnt pathways. Conclusions In summary, 25–50 mg/kg VC alleviated inhibitory effect of MT on immune-related genes in C. auratus liver, reducing MT-induced tissue damage. VC not only alleviated inflammation, oxidative stress, and immunotoxicity induced by MT through the regulation of the mTOR, MAPK, and Wnt signaling pathways, but also indirectly enhanced cellular antioxidant defense mechanisms by regulating the NRF2 pathway. This provides a theoretical basis for VC application in aquaculture, improving fish health and increasing efficiency.

Abstract Background Dynamic spasticity (DS) is a common complication post-spinal cord injury (SCI), marked by intermittent increases in muscle tone during postural transitions or movement. Despite its prevalence, high-quality research on DS incidence, risk factors, and underlying mechanisms in SCI patients remains limited. With the growing application of spinal cord stimulation (SCS) for spasticity control, the role of proprioception in DS development has garnered attention. Additionally, advances in diffusion tensor imaging (DTI) allow for the analysis of the reticulospinal tract’s (RST) role in postural control among SCI patients. However, the impact of microstructural changes in RST and proprioception on DS following SCI remains unclear. Objective To investigate the relationship between microstructural changes in the RST and proprioceptive circuits in SCI patients, exploring their association with DS and potential predictive factors that influence recovery. Methods This is a 12-month prospective cohort study. The neurophysiological and global functional status of the participants will be assessed. Primary outcomes include DTI indices of RST and proprioception, and spasticity assessment. Secondary outcomes include auditory startle reflex (ASR), H-reflex, shear wave velocity (SWV), overall functional status including spinal cord independence measure, gait analysis, modified Barthel Index, and the 36-item short form health survey. Data will be collected at 1, 3, 6, and 12 months after enrolment. Matched healthy controls will be measured during the same period after recruitment. Discussion This study is the first to explore the role of microstructural changes in the RST and proprioception in the assessment and prediction of DS following SCI. The findings aim to enhance theoretical understanding of SCS in spasticity management and to establish pre-treatment criteria for SCS interventions targeting motor function recovery in SCI. Trial registration number ChiCTR2400090724.

Abstract Background High-frequency ventilation (HFV) is commonly used in neonatal intensive care units to provide respiratory support for critically ill neonates. Currently, there is no standardized procedure for weaning from HFV. Two commonly used strategies are transitioning from HFV to conventional mechanical ventilation (CMV) before extubation (HFV-CMV) and extubation after decreasing mean airway pressure during HFV (HFV-HFV). The impact of these strategies on neonatal cerebral oxygenation and hemodynamics remains incompletely understood. Methods We will conduct a prospective, single-center, randomized controlled trial to investigate the effects of two different HFV weaning strategies (HFV-CMV, HFV-HFV) on neonatal cerebral oxygenation and hemodynamics. The patients enrolled in the trial will be randomly allocated to either the HFV-CMV group or the HFV-HFV group in a 1:1 ratio. The primary outcome will be cerebral oxygen saturation (ScO2) before and after the intervention. Second outcomes are cerebral fractional tissue oxygen extraction, heart rate, blood pressure, and the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia. We hypothesize that HFV-CMV results in positive impact on neonatal cerebral oxygenation compared to HFV-HFV. This study aims to identify a better weaning strategy for HFV and contribute evidence-based data to enhance its clinical application in newborns, potentially improving the care and outcomes for neonates receiving HFV. Discussion This study aims to assessing the impact of different HFV weaning strategies on neonatal cerebral oxygenation and hemodynamics, as well as the relationship between the duration of HFV under different strategies and neurological complications, to identify better weaning methods for HFV. We hope to contribute evidence-based data to enhance clinical application of HFV in newborns, potentially improving the care and outcomes for neonates receiving HFV. Trial registration Chinese Clinical Trial Registry: ChiCTR2400088628. Registered on August 22, 2024, https://www.chictr.org.cn/bin/project/edit?pid=235926 .

Abstract Objective To investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM). Methods A total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM. Results The AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P

Abstract Background With increasing age, the social and economic burdens of postmenopausal osteoporosis are steadily increasing. This study aimed to investigate the factors that influence the development of postmenopausal osteoporosis. Methods Postmenopausal women at the Affiliated Hospital of Jiangnan University from January 2023 to December 2023 were recruited for BMD examination. The patients were divided into a normal group, an osteopenia group and an osteoporosis group according to their T value. Questionnaires, including the Gastrointestinal Symptom Rating Scale and Short Form 12, were administered through face-to-face interviews. Bone turnover markers and serum protein levels of Fasting venous blood were detected. Results A total of 222 postmenopausal women met the inclusion criteria were recruited. Univariate analysis revealed statistically significant differences in age, education, BMI, supplementation with soy products, supplementation with dairy products, supplementation with other nutritional supplements, exercise frequency, gastrointestinal symptom score, quality of life, 25(OH)D, total protein, albumin and prealbumin among the three groups (P

Abstract Background Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS). Methods Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-𝜿B pathway related protein, and vascular density markers were determined. Results There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-𝜿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats. Conclusions Together, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS.

The prebiotic synthesis of peptides prior to ribosome-catalyzed processes remains an enigma. The synthesis of abiotic peptides from amino acids (AAs) is primarily constrained by high activation energies and unfavorable thermodynamics, necessitating the identification of plausible prebiotic alternatives for synthesizing prebiotic peptides. Here we present a plausible pathway to the formation of prebiotic peptides, wherein oligopeptides, oligopeptide amides, and cyclic oligopeptides can be directly synthesized from amino acid amides (AA-NH2) under wet–dry cycle conditions without the need for any enhancers. The subsequent investigation revealed that AA-NH2 demonstrated more favorable thermodynamic reaction effects than AAs in peptide formation. In contrast to the polymerization of AAs, the process of peptide formation through the polymerization of AA-NH2 was significantly simplified. Additionally, AA-NH2 was discovered to function as a “bridge” for the formation of peptides from AAs, thereby facilitating their participation in the synthesis of intricate peptide structures. On the basis of these findings, a plausible mechanism for the prebiotic origin network of peptides under primordial Earth conditions has been proposed. Overall, this research presents a plausible pathway for the generation of prebiotic peptides and peptide libraries within prebiotic environments.

Fructokinase (FRK) is a regulator of fructose signaling in plants and gateway proteins that catalyze the initial step in fructose metabolism through phosphorylation. Our previous study demonstrated that MdFRK2 protein exhibit not only high affinity for fructose, but also high enzymatic activity due to sorbitol. However, genome-wide identification of the MdFRK gene family and their evolutionary dynamics in apple are yet to be reported. A systematic genome-wide analysis in this study identified a total of nine MdFRK gene members, which could phylogenetically be clustered into seven groups. Chromosomal location and synteny analysis of MdFRKs revealed that their expansion in the apple genome is primarily driven by tandem and segmental duplication events. Divergent expression patterns of MdFRKs were observed in four source-sink tissues and at five different apple fruit developmental stages, which suggested their potential crucial roles in the apple fruit development and sugar accumulation. Reverse transcription-quantitative PCR (RT-qPCR) identified candidate NaCl or drought stress responsive MdFRKs, and transgenic apple plants overexpressing MdFRK2 exhibited considerably enhanced salinity tolerance. Our results will be useful for understanding the functions of MdFRKs in the regulation of apple fruit development and salt stress response.

Abstract Background Neonatal septic shock represents a critical and life-threatening condition that necessitates immediate and personalized interventions. Prior research endeavors have been undertaken to inform the optimization of neonatal septic shock management, yet substantial heterogeneity prevails in the selection, measurement, and reporting of outcomes across relevant studies. The heterogeneity in outcome selections and measures impedes the comparability of results and the synthesis of evidence, thus contributing to suboptimal utilization of research findings. This protocol presents the methodology for identifying and developing a Core Outcome Set for Neonatal Septic Shock Management (COS-NSS), intended for use in both research and routine clinical practice. A rigorous four-stage approach will be employed to develop the COS-NSS. In Stage 1, a scoping review will be conducted to compile a list of currently reported outcomes for neonatal septic shock management. Stage 2 will involve an expert stakeholder meeting using a semi-structured discussion approach to elucidate all identified outcomes and outcome domains, as well as to gather any additional outcomes. Moving to Stage 3, a two-round e-Delphi survey involving a wide variety of stakeholders will be undertaken to elicit diverse perspectives on the level of importance assigned to each proposed outcome. Finally, in Stage 4, the results of the Delphi study will be discussed in a consensus meeting to determine and agree on the final list of outcomes that will constitute the COS-NSS. Discussion The stagewise approach integrates research evidence with multi-stakeholder perspectives to establish standardized outcomes that would improve consistency across neonatal septic shock trials. The development and uptake of the COS-NSS will facilitate effective comparison of studies, allowing for study synthesis and generation of high-quality evidence, thus ultimately fostering enhanced medical care for neonates suffering from septic shock. Trial registration Core Outcome Measures in Effectiveness Trials (COMET) Initiative database registration: 2766 . Registered on July 19th, 2023.

Abstract Background Dental filling is a prevalent method for treating dental defects. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward dental defects and dental fillings among dental patients in Jinan, Shandong Province, China. Methods This cross-sectional study was conducted at the main campus and several branch campuses of Jinan Stomatological Hospital, and community locations within Jinan city between October 2023, and January 2024. Spearman correlation analysis and mediation analysis were used to assess the associations and interrelationships between KAP scores. Results In this study, 2529 dental patients participated, with 69.1% being females. Of these, 1711 had no dental defects, 551 had defects and fillings, and 267 had defects without fillings. Their median knowledge, attitude, and practice (Questions 1–6) scores were 8.00 [5.00, 12.00] (possible range: 0–18), 27.00 [26.00, 29.00] (possible range: 10–50), and 19.00 [15.00, 24.00] (possible range: 9–45), respectively. Mediation analysis revealed that in patients without dental defects, knowledge had a direct effect on attitude (β = -0.983, 95% CI: -0.999, -0.966, P

Abstract Plant height is a critical agronomic trait closely linked to yield, primarily regulated by Gibberellins (GA) and auxins, which interact in complex ways. However, the mechanism underlying their interactions remain incompletely understood. In this study, we identified a tomato mutant exhibiting significantly reduced plant height. Through gene cloning and bulked segregant analysis (BSA) sequencing, we found that the mutant gene corresponds to the tomato auxin response factor gene SlARF5/MP. Here, we show that overexpression of SlARF5/MP significantly enhances plant height. Additionally, treatment with GA3 restored the plant height of the mutant to wild-type (WT) levels, indicating that GA content is a key factor influencing plant height. We also observed significant upregulation of GA-biosynthesis genes, including GA2-oxidases GA20ox3 and GA20ox4, as well as the GA3 biosynthesis gene GA3ox1, in SlARF5-overexpressing plants. Furthermore, we demonstrated that SlARF5 directly binds to SlGA2ox3, which mediates the conversion of GA3 to inactive GA, therebyregulating its expression. Our findings suggest that SlARF5 modulates GA3 metabolism by regulating GA synthesis genes, ultimately leading to alterations in plant height.

Abstract As the role of RNA modification in gene expression regulation and human diseases, the “epitranscriptome” has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A modification is the most common post-transcriptional modification of eukaryotic mRNA, accounting for 80% of RNA methylation modifications. At the same time, several other modifications of RNA, such as N1-methyladenosine (m1A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), pseudouridine (Ψ) and N7-methylguanosine (m7G) have also been demonstrated to be involved in cancer and drug resistance. This review mainly discusses the research progress of RNA modifications in the field of cancer and drug resistance and targeting of m6A regulators by small molecule modulators, providing reference for future study and development of combination therapy to reverse cancer drug resistance.

Abstract Background In patients undergoing breast-conserving therapy without surgical clip implantation, the accuracy of tumor bed identification and the consistency of clinical target volume (CTV) delineation under computed tomography (CT) simulation remain suboptimal. This study aimed to investigate the feasibility of implementing preoperative magnetic resonance (MR) simulation on delineations by assessing interobserver variability (IOV). Methods Preoperative MR and postoperative CT simulations were performed in patients who underwent breast-conserving surgery with no surgical clips implanted. Custom immobilization pads were used to ensure the same supine position. Three radiation oncologists independently delineated the CTV of tumor bed on the images acquired from MR and CT simulation registration and CT simulation alone. Cavity visualization score (CVS) was assigned to each patient based on the clarity of the tumor bed on CT simulation images. IOV was indicated by generalized conformity index (CIgen), denoted as CIgen−CT and CIgen−MR/CT, and the distance between the centroid of mass (dCOM), denoted as dCOMCT and dCOMMR/CT. The variation of IOV in different CVS subgroups was analyzed. Results A total of 10 patients were enrolled in this study. The median and interquartile range (IQR) of maximum pathological diameter of the tumors in all patients were 1.55 (0.80–1.92) cm. No statistical significance was found between the volumes of CTVs on CT simulation and on MR/CT simulation registration images (p = 0.387). CIgen−MR/CT was significantly larger than CIgen−CT (p = 0.005). dCOMMR/CT was significantly smaller than dCOMCT (p = 0.037). The median and IQR of CVS in all patients were 2.34 (2.00–3.08). The difference of CIgen between CIgen−MR/CT and CIgen−CT was larger in the low CVS group (p = 0.016). The difference of dCOM showed a decreasing trend when CVS was lower, although it did not reach statistical significance (p = 0.095). Conclusions For patients who underwent breast-conserving surgery without surgical clip implantation, the use of preoperative MR simulation in delineating the CTV of tumor bed decreased the IOV among observers. The consistency of tumor bed identification was improved especially in cases where the margins of tumor bed were challenging to visualize on CT simulation images. The study findings offer potential benefits in reducing local recurrence and minimizing tissue irritation in the surrounding areas. Future investigation in a larger patient cohort to validate our results is warranted.

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. Methods Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1’s impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. Results Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. Conclusions GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.

Owing to the production of lignin-modifying enzymes (LMEs), white-rot fungi (WRF) such as polypores are potent organisms in the biodegradation of xenobiotic pollutants. The nonspecific function of LMEs including laccase and manganese peroxidase (MnP), has enabled the use of WRF in biotechnological applications, particularly in bioremediation. In this study, 12 strains from nine white-rot basidiomycete genera viz., Ganoderma, Inocutis, Irpex, Lentinus, Lenzites, Oxyporus, Peniophora, Sanghuangporus, and Trametes were isolated from Iran and identified using morphological and molecular tools. The enzyme activity of laccase and manganese peroxidase that directly correlated with the biodegradation were determined, and the strains with the highest enzyme activities were evaluated for their ability to degrade 400 mg/L of anthracene over 28 days. Gas chromatography with flame ionization detector (GC-FID) revealed that four polypores viz., Trametes versicolor v21te, T. versicolor v22da, T. hirsuta, and Oxyporus sp. degraded 64%, 52%, 34%, and 20% of the anthracene, respectively. According to our analysis, the examined indigenous WRF are potentially useful candidates for the development of new mycoremediation techniques to degrade polycyclic aromatic hydrocarbons (PAHs).

Abstract This paper explores the mapping from specific digitalization practices to specific resilient performance against a great shock. Based on an adapted structure–conduct–performance framework, this paper hypothesizes by theoretically analyzing how the pre-shock establishment of digital retailing practices could trigger physical retailers’ bounce-back and bounce-forward performance against the COVID-19 crisis. Using a difference-in-differences strategy, the hypotheses are examined with a sample including 549 observations of 50 Chinese listed retailers from the first quarter of 2018 to the third quarter of 2020. The empirical results mainly indicate the following binary findings. First, regardless of the differences in triggering bounce-back performance, different digital retailing practices are found to be effective in triggering physical retailers’ bounce-forward performance against the COVID-19 crisis. This somewhat addresses the concern about the temporality of digitalization-enabled resilience by revealing the generality across digital retailing practices in the sense of triggering resilient performance. Second, it is shown that physical retailers’ bounce-back performance at a specific stage of the COVID-19 crisis could only be triggered by digital retailing practices that coincidentally apply to the shock-induced market structure changes at the stage. The results emphasize each digitalization practice’s individuality in triggering resilient performance. This justifies the non-negligibility of the direct mapping from specific digitalization practices to specific resilient performance in digitalization-enabled resilience evaluation.

Abstract This study aims to identify colorectal cancer (CRC)-related proteomic profiles and develop a prediction model for CRC onset by integrating proteomic profiles with genetic and non-genetic factors (QCancer-15) to improve the risk stratification and estimate of personalized initial screening age. Here, using a two-stage strategy, we prioritize 15 protein biomarkers as predictors to construct a protein risk score (ProS). The risk prediction model integrating proteomic profiles with polygenic risk score (PRS) and QCancer-15 risk score (QCancer-S) shows improved performance (C-statistic: 0.79 vs. 0.71, P = 4.94E–03 in training cohort; 0.75 vs 0.69, P = 5.49E–04 in validation cohort) and net benefit than QCancer-S alone. The combined model markedly stratifies the risk of CRC onset. Participants with high ProS, PRS, or combined risk score are proposed to start screening at age 46, 41, or before 40 years old. In this work, the integration of blood proteomics with PRS and QCancer-15 demonstrates improved performance for risk stratification and clinical implication for the derivation of risk-adapted starting ages of CRC screening, which may contribute to the decision-making process for CRC screening.

Abstract We investigate the meson-baryon interaction in coupled channels with the quantum numbers of the pentaquarks $$P_{bss}$$ P bss and $$P_{bsss}$$ P bsss . The interaction is derived from an extension of the local hidden gauge approach to the heavy quark sector, which has demonstrated accurate results compared to experiments involving $$\Omega _{b}$$ Ω b , $$\Xi _{b}$$ Ξ b states, and pentaquarks $$P_{c}$$ P c and $$P_{cs}$$ P cs . In our study, we identify several molecular states with small decay widths within the chosen set of coupled channels. The spin-parity ( $$J^P$$ J P ) of these states is as follows: $$J^P={\frac{1}{2}}^-$$ J P = 1 2 - for pseudoscalar-baryon ( $${\frac{1}{2}}^+$$ 1 2 + ) coupled channels, $$J^P={\frac{3}{2}}^-$$ J P = 3 2 - for pseudoscalar-baryon ( $${\frac{3}{2}}^+$$ 3 2 + ) coupled channels, $$J^P={\frac{1}{2}}^-$$ J P = 1 2 - and $${\frac{3}{2}}^-$$ 3 2 - for vector-baryon ( $${\frac{1}{2}}^+$$ 1 2 + ) coupled channels, and $$J^P={\frac{1}{2}}^-$$ J P = 1 2 - , $${\frac{3}{2}}^-$$ 3 2 - , $${\frac{5}{2}}^-$$ 5 2 - for vector-baryon ( $${\frac{3}{2}}^+$$ 3 2 + ) coupled channels. We search for the poles of these states and evaluate their couplings to the different channels.

Abstract Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with αPD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA) in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous H2O2. All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8+ T cells in tumor. At the same time, the combination with αPD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe3+, which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy.

Abstract Mid-infrared (MIR) fiber lasers are important for a wide range of applications in sensing, spectroscopy, imaging, defense, and security. Some progress has been made in the research of MIR fiber lasers based on soft glass fibers, however, the emission range of rare-earth ions and the robustness of the host materials are still a major challenge for MIR fiber lasers. The large number of gases provide a variety of optical transitions in the MIR band. When combined with recent advances in low-loss hollow-core fiber (HCF), there is a great opportunity for gas-filled fiber lasers to further extend the radiation to the MIR region. Here, a 4.8-μm CO-filled silica-based HCF laser is reported for the first time. This is enabled by an in-house manufactured broadband low-loss HCF with a measured loss of 1.81 dB/m at 4.8 μm. A maximum MIR output power of 46 mW and a tuning range of 180 nm (from 4644 to 4824 nm) are obtained by using an advanced 2.33-μm narrow-linewidth fiber laser. This demonstration represents the longest-wavelength silica-based fiber laser to date, while the absorption loss of bulk silica at 4824 nm is up to 13, 000 dB/m. Further wavelength expansion could be achieved by changing the pump absorption line and optimizing the laser structure.

Abstract. Background:. Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants. Methods:. A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of

Abstract The study aimed to assess the prospective associations between sleep duration, sleep restfulness, midday napping and hip fracture (HF) and falls in a nationally representative Chinese population. Data were from the China Health and Retirement Longitudinal Study which was conducted from 2013 to 2018. In total, 10,508 individuals without a history of HF in 2013 were included. Nighttime sleep duration, sleep restfulness and midday napping were self-reported. Logistic regression analyses were performed to examine the relationships between sleep problems and HF as well as falls, adjusting for covariates. A total of 313 (3.0%) participants reported HF, and 3899 (37.1%) experienced at least one fall event over the following 5-year period. Participants who had a short sleep duration (≤ 6) were more likely to report HF (OR = 1.27, 95% CI = 1.00-1.62) and falls (OR = 1.18, 95% CI = 1.07–1.30) than those who had a normal sleep duration (6–9 h) in the fully adjusted model. Participants having unrestful sleep were also more likely to report falls (OR = 1.23, 95% CI = 1.11–1.36) than those who had restful sleep. However, there was no significant association between midday napping and HF and falls. In conclusion, short sleep duration and sleep restfulness were independently associated with an increased risk of HF and falls, which may have important clinical and public health implications. Interventions to improve sleep quality may reduce the risk of HF and fall accidents among middle-aged and older people.