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Yan Xing,1,* Rui Jing,2,* Xiaoying Tang,2 Zhenqi Jiang2 1Department of Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 2School of Medical Technology, Beijing Institute of Technology, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenqi Jiang; Xiaoying Tang, Email jiangzhenqi@bit.edu.cn; xiaoying@bit.edu.cnObjective: Ovarian cancer cells are prone to acquire tolerance to chemotherapeutic agents, which seriously affects clinical outcomes. The development of novel strategies to enhance the targeting of chemotherapeutic agents to overcome drug resistance and minimize side effects is significant for improving the clinical outcomes of ovarian cancer patients.Methods: We employed folic acid (FA)-modified ZIF-90 nanomaterials (FA-ZIF-90) to deliver the chemotherapeutic drug, cisplatin (DDP), via dual targeting to improve its targeting to circumvent cisplatin resistance in ovarian cancer cells, especially by targeting mitochondria. FA-ZIF-90/DDP could rapidly release DDP in response to dual stimulation of acidity and ATP in tumor cells.Results: FA-ZIF-90/DDP showed good blood compatibility. It was efficiently taken up by human ovarian cancer cisplatin-resistant cells A2780/DDP and aggregated in the mitochondrial region. FA-ZIF-90/DDP significantly inhibited the mitochondrial activity and metastatic ability of A2780/DDP cells. In addition, it effectively induced apoptosis in A2780/DDP cells and overcame cisplatin resistance. In vivo experiments showed that FA-ZIF-90/DDP increased the accumulation of DDP in tumor tissues and significantly inhibited tumor growth.Conclusion: FA-modified ZIF-90 nanocarriers can improve the tumor targeting and anti-tumor effects of chemotherapeutic drugs, reduce toxic side effects, and are expected to be a novel therapeutic strategy to reverse drug resistance in ovarian cancer.Keywords: ovarian cancer, drug resistance, targeted therapy, folic acid, ZIF-90, nanomedicine, mitochondria, cell apoptosis

Rui Jing,1 Hui Dong,1 Kun Huang,2 Zhong Liu,1 Ran Xue,1 Yiran Dong,1 Mei Jiao,3 Na Li,4 Yumei Guo,5 Yun Liu,6 Wenqian Zhang,1 Hongyun Sun1 1Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China; 2Tuberculosis Control Division, Licheng Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Department of Sexually Transmitted Diseases and AIDS Prevention and Control, Lixia Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Tuberculosis and Vector Control Division, Shizhong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 5Department of Infectious Diseases and Endemic Disease Control, Huaiyin Center for Disease Control and Prevention, Jinan, People’s Republic of China; 6AIDS Prevention and Control Department, Tianqiao Center for Disease Control and Prevention, Jinan, People’s Republic of ChinaCorrespondence: Wenqian Zhang; Hongyun Sun, Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China, Tel +86 0531-81278897 ; +86 0531 81278873, Email wqzh618@gmail.com; jncdcxxtb@jn.shandong.cnPurpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population.Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects.Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥ 65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥ 6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group.Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.Keywords: pulmonary tuberculosis, awareness rate, completed treatment patients, layered analysis

Yuanbo Wang1,2 *, Xia Li1,2 *, Rui Jing,2 Wenshan Yang,1,2 Yichen Wang,1,2 Chaochen Wang,1,2 Lei Yao,1,2 Xiaoming Cui,3 Yuan Hu2 1Graduate School of PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Health Medicine, The Third Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoming Cui, Department of Health Medicine, The Third Medical Center of PLA General Hospital, Beijing, 100039, People’s Republic of China, Email 18611206336@163.com Yuan Hu, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, No. 28 FuXing Road, Beijing, 100853, People’s Republic of China, Email huyuan1980619@126.comPurpose: Tryptophan metabolism is involved in the etiology and exacerbation of depressive disorders. Kai-Xin-San (KXS), a traditional Chinese medicine formula, has been widely used to treat depression and modulate serotonin simultaneously, but how it regulates depressive-like behavior by shifting the balance of the tryptophan-serotonin metabolism and kynurenine pathway remains vague.Patients and Methods: Ten participants with mild to moderate depression treated with KXS (KXS preparation) were analyzed in this study. Depression rating scale score and the concentration of serum tryptophan, 5-hydroxytryptophan and kynurenine was measured at baseline and the endpoint of KXS treatment. To explore the specific regulatory mechanism of KXS in tryptophan metabolism, the chronic restraint stress (CRS) was used to induce depressive-like syndrome in rats and the hippocampus level of tryptophan, 5-hydroxytryptophan, kynurenine with downstream metabolites (kynurenic acid, quinolinic acid) and key enzymes (indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase, kynurenine aminotransferase) were analyzed by liquid chromatography–electros pray ionization tandem mass spectrometry, high performance liquid chromatography and enzyme-linked immunosorbent assay respectively.Results: KXS significantly decreased depression rating scale scores and increased the serum tryptophan and kynurenine concentration in depressive patients compared to baseline. Also, it alleviated the depressive behavior in CRS rats obviously. Comparing with CRS group, KXS increased tryptophan, 5-hydroxytryptophan, kynurenine level in rat hippocampus. Furthermore, in kynurenine pathway, KXS decreased the expression of indoleamine 2,3-dioxygenase, increased kynurenic acid by upregulating the expression of kynurenine aminotransferase while decreased quinolinic acid level in hippocampus, which suggested that KXS more favored improving serotonin pathway, and neuroprotective kynurenic acid branch in the tryptophan metabolism.Conclusion: This is the first tryptophan metabolomic study of patients with depression undergoing KXS treatment. Combining these clinical results with CRS induced rat model studies, it verified that KXS achieves an excellent antidepressant effect and balances tryptophan-kynurenine metabolic pathways by regulating some key metabolic products and enzymes.Keywords: depression, amino acids, TCM, KaiXinSan

Rongxin Zhang,1,2 Zhao Hou,2 Kexin Liao,2 Chao Yu,2 Rongrong Jing,1,2 Caixia Tu1,2 1Institute of Integrative Medicine, Dalian Medical University, Dalian, 116044, People’s Republic of China; 2Department of Dermatology, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of ChinaCorrespondence: Caixia Tu, Department of Dermatology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, 116027, People’s Republic of China, Tel +8617709872288, Fax +86 411 84672130, Email tucx2010@sina.comPurpose: Circular RNAs (circRNAs) are abundant, stable, and evolutionarily conserved noncoding RNAs with impacts on cell proliferation, differentiation, invasion, apoptosis, and immunity by acting as an miRNA sponge. This study aimed to investigate the expression of circRNAs in vitiligo and analyze the differentially expressed circRNAs (DEcircRNAs) bioinformatically.Patients and Methods: Biopsies of five lesional and five nonlesional skins of patients with vitiligo and five healthy skins (control) were harvested in this study. The expression profiles of circRNAs and DEcircRNAs were determined by microarray analysis and qRT-PCR. Bioinformatics analysis was used to predict target genes of DEcircRNAs binding to miRNAs and their underlying functions. Meanwhile, a competing endogenous RNA (ceRNA) network was constructed using Cytoscape.Results: A total of 817 and 508 DEcircRNAs were identified in lesional and nonlesional skins of patients with vitiligo, respectively. The results of hsa_circRNA_000957 and hsa_circRNA_101798 validation were consistent with our microarray analysis. Furthermore, 32 miRNA response elements (MREs) and related target genes of DEcircRNAs were identified, whose main functions were involved in the pathogenesis of vitiligo. Hsa_circRNA_000957 and hsa_circRNA_101798 might be candidate biomarkers for vitiligo.Conclusion: This study provides scientific clues for understanding the mechanism of vitiligo.Keywords: vitiligo, circular RNAs, microRNAs, miRNA response element, ceRNA

Ran Jing,1– 3 Ian Morrissey,4 Meng Xiao,1,3 Tian-Shu Sun,3,5 Ge Zhang,1,3 Wei Kang,1,3 Da-Wen Guo,6 Jalal A Aram,7 Jeffrey Wang,8 Eric A Utt,7 Yao Wang,1,3 Ying-Chun Xu1– 3 1Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of China; 4IHMA Europe Sarl, Monthey, Valias, Switzerland; 5Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Laboratory Medicine, the First Clinical Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Medical Affairs, Pfizer Inc, Groton, CT, USA; 8Clinical Development, Pfizer, Beijing, People’s Republic of ChinaCorrespondence: Ying-Chun Xu; Yao Wang, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Number 1, Shuaifuyuan Road, Dongcheng District, Beijing, People’s Republic of China, Fax +86 10 69159766, Email xycpumch@139.com; yaoo_wang@163.comPurpose: Monitoring antifungal susceptibility patterns for new or established antifungals is imperative. Antifungal resistance is frequent in molds, frequently leading to invasive mold infections (IMIs) in immunocompromised patients with high morbidity and mortality. Limited availability of effective antifungals for treatment of IMIs in China is an enormous challenge. The purpose of this study was to monitor in vitro antifungal resistance profiles of mold isolates from China, with a particular focus on evaluating in vitro isavuconazole (ISA) activity against these isolates, contributing to the treatment guidance in clinics.Methods: We evaluated the in vitro activity of ISA and its comparators (voriconazole [VOR] and amphotericin B [AMB]) against 131 clinical isolates of Aspergillus spp. (n = 105) and Mucorales order (n = 26) collected between 2017 and 2020 from China.Results: ISA and VOR exhibited similar in vitro activity against Aspergillus spp., with minimum inhibitory concentration (MIC)50 of 1 μg/mL and MIC90 of 2 μg/mL, respectively. Overall, AMB was less active than azoles against Aspergillus spp. (MIC50: 4 μg/mL, MIC90: 8 μg/mL). Against the Mucorales order, ISA demonstrated MIC50 of 0.5 μg/mL and MIC90 of 1 μg/mL; however, one strain each of Mucor circinelloides and Syncephalastrum racemosum were resistant to ISA (MICs: > 8 μg/mL). VOR exhibited little or no activity (MIC50: 8 μg/mL, MIC90: > 8 μg/mL) against the Mucorales order, whereas AMB had MIC50 and MIC90 of 1 μg/mL.Conclusion: This was the first multicenter, in vitro study conducted in China and demonstrated the excellent activities of ISA against most species of the Mucorales order. MIC indicated an advantage over currently available azole antifungals, positioning ISA as a potential alternative to VOR for clinical management of IMIs. As with other antimicrobials, clinicians should employ stewardship and best practices in relation to potential resistance to new azole antifungals.Keywords: Mucorales order, Aspergillus species, antifungal susceptibility testing, isavuconazole, resistance

Songwei Lv,1,* Ran Jing,2,* Xiaowu Liu,3,4 Honglei Shi,3,4 Yunfeng Shi,3,4 Xugang Wang,3,4 Xiubo Zhao,1,5 Kai Cao,3,4 Zhong Lv3,4 1School of Pharmacy, Changzhou University, Changzhou, 213164, People’s Republic of China; 2Division of Nephrology, The Affiliated Changzhou NO. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213164, People’s Republic of China; 3Department of Urology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213164, People’s Republic of China; 4Department of Urology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, 213164, People’s Republic of China; 5Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD, UK*These authors contributed equally to this workCorrespondence: Kai Cao; Zhong Lv Email caokai9001@126.com; lzabc0105@163.comIntroduction: Cancer of the bladder is one of the most common and life-threatening. Compared with traditional delivery methods, intravesical administration reduces the amount of drugs required, increases the amount of drugs reaching the lesion site, and minimizes systemic exposure to therapeutic agents. To overcome the limitations of urinary voiding, low urothelium permeability, and intermittent catheterization for large dilution and irrigation of drugs in the bladder, magnetic and photothermal-responsive folate receptor-targeted thermal liposomes (FA-TMLs) were designed for the targeted delivery of doxorubicin (DOX) to bladder cancer cells.Methods: Through a microfluidic mixer chip, the magnetic nanoparticles (MNPs), gold nanorods (GNRs) and DOX were encapsulated in folate-modified thermosensitive liposomes to form FA-TMLs@MNPs-GNRs-DOX. DLS, TEM, DSC, and magnetic hysteresis loop were used to characterize the construction of FA-TMLs@MNPs-GNRs-DOX.Results: FA-TMLs@MNPs-GNRs-DOX had a size of about 230 nm and exhibited superparamagnetic properties with the saturation magnetization of 20 emu/g. The DOX loading capacity was as high as 0.57 mg/mL. Additionally, drug release of the FA-TMLs@MNPs-GNRs-DOX could be controlled by temperature change through the photothermal effect. A 980 nm laser beam was selectively irradiated on the FA-TMLs@MNPs-GNRs-DOX to trigger the structural changes of the FA-TMLs, and an average of 95% of the drug was released after 3 hours. The results of cell uptake experiments reveal indicated that FA-TMLs@MNPs-GNRs-DOX were able to specifically bind folate-receptor-positive cells and exhibited toxicity to bladder tumor cells.Conclusion: The present results suggest FA-TMLs@MNPs-GNRs-DOX have a promising multifunctional response and can act as an ideal multifunctional drug delivery system (DDS) for the treatment of bladder tumors.Keywords: bladder cancer, drug delivery, magnetic response, thermo-sensitive liposomes, folate-targeted, photothermal effect

Yang Luo,1,* Min-Hao Yu,1,* Yi-Zhou Huang,1 Ran Jing,1 Jun Qin,1 Shao-Lan Qin,1 Jay N Shah,1,2 Ming Zhong1 1Department of Gastrointestinal Surgery, Renji Hospital, Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Department of Surgery, Patan Hospital, Patan Academy of Health Sciences, Lalitpur, Kathmandu, 44700, Nepal*These authors contributed equally to this workCorrespondence: Ming Zhong; Jay N Shah Email drzhongming@hotmail.com; drjaywufei@gmail.comBackground: Preservation of the left colic artery in low-tie (LT) of inferior mesenteric artery remains controversial compared to high-tie (HT) in the colon and rectal cancers, for lymph node dissection, anastomotic leakage, and oncological outcome. This cohort study aims to analyze short- and long-term outcomes of laparoscopic anterior resections in LT vs HT for rectal cancers.Methods: We analyzed a cohort of laparoscopic AR for RC from 2013 to 2016 at Renji Hospital, Shanghai, China. Short- and long-term outcome in LT vs HT group were compared for clinico-demographic characteristics, operative-time, lymph node dissection, short-term 30-day outcome, and long-term 3- and 5-year overall survival as well as disease-free survival. The x2, t-test, and logistic regressions analysis were used and p< 0.05 was considered significant.Results: The cohort consisted of 614 laparoscopic AR with LT (236) and HT (378). The clinicodemographic characteristics were comparable among the groups. The surgery took longer in LT. The yield of LND was similar. Leakage occurred in 12.21% (n=75). Leakage was fewer in LT than HT, 8.89% vs 14.28%, p=0.047. The postoperative severe complications were higher in HT. The 30-day mortality was nil. The long-term 3- and 5-year overall survival and disease-free survival were similar in LT and HT.Conclusion: The LT with preservation of left colic artery had similar lymph node yield, but lower leakage and complications than HT in laparoscopic anterior resections for rectal cancers. The long-term 3- and 5-year overall and disease-free survival were similar in the two groups.Keywords: anastomotic leakage, Clavien-Dindo complications, laparoscopic anterior resection, left colic artery, low-tie high-tie of the inferior mesenteric artery, rectal cancer

Rize Jing,1,2 Tingting Xu,1,3 Hongguo Rong,2 Xiaozhen Lai,1 Hai Fang2,4,5 1School of Public Health, Peking University, Beijing 100083, People’s Republic of China; 2China Center for Health Development Studies, Peking University, Beijing 100083, People’s Republic of China; 3Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts 02115, USA; 4Peking University Health Science Center- Chinese Center for Disease Control and Prevention Joint Center for Vaccine Economics, Peking University, Beijing 100083, People’s Republic of China; 5Key Laboratory of Reproductive Health, National Health Commission of the People’s Republic of China, Peking University, Beijing 10083, People’s Republic of ChinaCorrespondence: Hai FangChina Center for Health Development Studies, Peking University, Xueyuan Road 38, Mailbox 505, Haidian District, Beijing 100083, People’s Republic of ChinaTel +86-108-280-5702Fax +86-108-280-5695Email hfang@hsc.pku.edu.cnAim: This study aimed to evaluate the longitudinal association between sleep duration and depressive symptoms among the elderly in China.Methods: A data set from China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013 and 2015 was adopted with a total of 22,847 respondents aged ≥ 60-years-old. A linear regression analysis with generalized estimating equations was employed to examine the longitudinal associations between duration of total sleep, nighttime sleep and daytime nap, and depressive symptoms.Results: An extra hour of total sleep including nighttime sleep and daytime nap was associated with lower incidence of depressive symptoms among the elderly after adjusting all confounders (OR=0.83, 95% CI: 0.82– 0.84). In addition, an extra hour of nighttime sleep (OR=0.82, 95% CI: 0.80– 0.83) or daytime nap (OR=0.93, 95% CI: 0.89– 0.97) was also negatively associated with depressive symptoms among the elderly. After controlling the total sleep time, an extra hour of nighttime sleep was negatively associated with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92), while an extra hour of daytime nap displayed a positive association with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92). Compared with the moderate nappers, only extended nappers had significantly higher incidence of depressive symptoms (OR=1.32, 95% CI: 1.19 to 1.45).Conclusion: For the elderly in China, increasing their total sleep, nighttime sleep, and/or daytime nap duration would reduce the incidence of depressive symptoms. Moreover, after fixing the total sleep time, increasing nighttime sleep was more beneficial to the decrease of the incidence of depressive symptoms than daytime nap.Keywords: sleep duration, daytime nap, depressive symptoms, China, the elderly

Abstract To investigate physiological function of α-synuclein is important for understanding its pathophysiological mechanism in synucleinopathies including Parkinson’s disease. Employing knockout mice, we found that Snac/α-synuclein deletion induced aberrant projection of olfactory sensory neurons and hyposmia. We identified 9 axon guidance associated differentially expressed proteins using iTRAQ based Liquid Chromatograph Mass Spectrometer. NCK2 is most significantly down-regulated protein among them. We further found that either α-synuclein deletion or NCK2 deficiency induced Eph A4 inactivation. Re-expressing Snac/α-synuclein in its knockout neurons reversed the down-regulation of NCK2, as well as the inactivation of EphA4. Overexpression of Snac/α-synuclein in α-synuclein deleted mice reversed the down-regulation of NCK2 and pEphA4, and improved the olfactory impairment of mice. Correlation analysis showed that there is a significant correlation between the protein level of α-synuclein, NCK2, and pEphA4, respectively. Nonetheless, immunoprecipitation analysis showed that NCK2 was associated with both EphA4 and Rho A, suggesting that NCK2 as a scaffolding protein to modulate Eph A4/Rho A pathway. Moreover, Rho A activity was significantly lower in α-synuclein deficient mice. Thus, α-synuclein regulates olfactory neurons projection through NCK2 dependent EphA4/Rho A pathway. Malfunction of α-synuclein because of deletion may cause aberrant olfactory neurons projection. This extended our knowledge of α-synuclein functions, which may explain why olfaction is usually impaired in some synucleinopathies.

Abstract Approximately 200 critically ill infants and children in New Zealand are in high-dependency care, many suspected of having genetic conditions, requiring scalable genomic testing. We adopted an acute care genomics protocol from an accredited laboratory and established a clinical pipeline using Oxford Nanopore Technologies PromethION 2 solo system and Fabric GEM™ software. Benchmarking of the pipeline was performed using Global Alliance for Genomics and Health benchmarking tools and Genome in a Bottle samples (HG002-HG007). Evaluation of single nucleotide variants resulted in a precision and recall of 0.997 and 0.992, respectively. Small indel identification approached a precision of 0.922 and recall of 0.838. Large genomic variations from Coriell Copy Number Variation Reference Panel 1 were reliably detected with ~2 M long reads. Finally, we present results obtained from fourteen trio samples, ten of which were processed in parallel with a clinically accredited short-read rapid genomic testing pipeline (Newborn Genomics Programme; NCT06081075; 2023-10-12).

Abstract Grain boundary hardening and precipitation hardening are important mechanisms for enhancing the strength of metals. Here, we show that these two effects can be amplified simultaneously in nanocrystalline compositionally complex alloys (CCAs), leading to near-theoretical strength and large deformability. We develop a model nanograined (TiZrNbHf)98Ni2 alloy via thermodynamic design. The Ni solutes, which has a large negative mixing enthalpy and different electronegativity to Ti, Zr, Nb and Hf, not only produce Ni-enriched local chemical inhomogeneities in the nanograins, but also segregate to grain boundaries. The resultant alloy achieves a 2.5 GPa yield strength, together with work hardening capability and large homogeneous deformability to 65% compressive strain. The local chemical inhomogeneities impede dislocation propagation and encourage dislocation multiplication to promote strain hardening. Meanwhile, Ni segregates to grain boundaries and enhances cohesion, suppressing the grain growth and grain boundary cracking found while deforming the reference TiZrNbHf alloy. Our alloy design strategy thus opens an avenue, via solute decoration at grain boundaries combined with local chemical inhomogeneities inside the grains, towards ultrahigh strength and large plasticity in nanostructured alloys.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) has significant productivity and economic impacts in swine herds. Accurately determining the PRRSV status at the herd level is crucial for producers and veterinarians to implement strategies to control and eliminate the virus from infected herds. This study collected oropharyngeal swabs (OSs), nasal swabs (NSs), oral fluid swabs (OFs), rectal swabs (RSs), and serum samples continuously from PRRSV challenged pigs under experimental conditions and growing pigs under field conditions. Additionally, OSs and serum samples were collected from individual sows from 50 large-scale breeding farms, and the collection of OSs does not require the sows to be restrained. Ct values of PRRSV were detected in all samples using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Results In PRRSV challenged pigs, OSs showed a higher PRRSV-positive rate until the end of the observation period. The Ct values of OSs were significantly lower than those of NSs, OFs, and RSs at 2, 8, 12, 14 and 20 days post-challenge (DPC) (P

The Open-Radio Access Network (O-RAN) alliance is leading the evolution of telecommunications towards a greater intelligence, openness, virtualization, and interoperability within mobile networks. The O-RAN standard incorporates of many components the Open-Central Unit (O-CU) and Open-Distributed Unit (O-DU), network slicing and heterogeneous base stations (BS). Together, these innovations have given rise to a three-tiered user association (UA) relationship in a type of network called heterogeneous network (HetNet) with network slicing-enabled. There is an absence of efficient UA schemes for achieving fair resource allocation in such network scenario. Hence, this study formulates the fairness-aware UA problem as a utility-based combinatorial optimization problem, which is computationally hard to solve. Hence, an efficient Binary Particle Swarm Optimization (BPSO)-based UA scheme is proposed to solve the problem. Through simulations of an O-RAN based HetNet with network slicing-enabled, performance of the proposed BPSO-UA scheme is compared against two other baseline UA schemes. Results demonstrate the effectiveness of the proposed BPSO-UA scheme in achieving high fairness through equitable network slicing resource allocation, thereby leading to higher user connectivity rate and comparable average spectral efficiency. This innovative approach sheds light on the potential of metaheuristic algorithms in tackling intricate UA challenges, offering valuable insights for the future design and optimization of mobile networks.

Abstract Objective This study aimed to develop and validate a nomogram for assessing the risk of nosocomial infections among obstetric inpatients, providing a valuable reference for predicting and mitigating the risk of postpartum infections. Methods A retrospective observational study was performed on a cohort of 28,608 obstetric patients admitted for childbirth between 2017 and 2022. Data from the year 2022, comprising 4,153 inpatients, were utilized for model validation. Univariable and multivariable stepwise logistic regression analyses were employed to identify the factors influencing nosocomial infections among obstetric inpatients. A nomogram was subsequently developed based on the final predictive model. The receiver operating characteristic (ROC) curve was utilized to calculate the area under the curve (AUC) to evaluate the predictive accuracy of the nomogram in both the training and validation datasets. Results The gestational weeks > = 37, prenatal anemia, prenatal hypoproteinemia, premature rupture of membranes (PROM), cesarean sction, operative delivery, adverse birth outcomes, length of hospitalization (days) > 5, CVC use and catheterization of ureter were included in the ultimate prediction model. The AUC of the nomogram was 0.828 (0.823, 0.833) in the training dataset and 0.855 (0.844, 0.865) in the validation dataset. Conclusion Through a large-scale retrospective study conducted in China, we developed and independently validated a nomogram to enable personalized postpartum infections risk estimates for obstetric inpatients. Its clinical application can facilitate early identification of high-risk groups, enabling timely infection prevention and control measures.