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Keyang Li,1,* Debao Li,2,* Hongliang Dong,1 Dongmei Ren,2 Dandan Gong,1 Shubo Wang,1 Yang Li,1 Yuanyuan Wu,1 Jikang Yang,3 Wenjuan Yan,4 Yi Li4 1Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Infectious Diseases Department, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi Li, Department of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7#, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15225061830 ; +86 15939039006, Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Since the introduction of ceftazidime–avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols.Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate.Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality.Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.Keywords: ceftazidime-avibactam, carbapenem-resistant gram-negative bacteria, combination therapy K. pneumoniae carbapenemase

Binbin Liu,1,* Pan Su,1,* Peilei Hu,1,* Mi Yan,1 Wenbin Li,1 Songlin Yi,1 Zhenhua Chen,1 Xiaoping Zhang,1 Jingwei Guo,1 Xiaojie Wan,1 Jue Wang,1 Daofang Gong,1 Hua Bai,1 Kanglin Wan,2 Haican Liu,2 Guilian Li,2 Yunhong Tan1 1Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China; 2National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunhong Tan, Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China, Tel +86-13874947876, Email Tanyunhong@163.com Guilian Li, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China, Tel +86-18519886112, Email liguilian@icdc.cnBackground: China is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB). However, published data on pyrazinamide (PZA) resistance are still limited in Hunan province, China. This study investigated the prevalence, transmission, and genetic diversity of PZA resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Hunan province.Methods: Drug susceptibility testing (DST) with the Bactec MGIT 960 PZA kit and pyrazinamidase (PZase) testing were conducted on all 298 MDR clinical isolates. Moreover, 24-locus MIRU-VNTR and DNA sequencing of pncA, rpsA, and panD genes were conducted on 180 PZA-resistant (PZA-R) isolates.Results: The prevalence of PZA resistance among MDR-TB strains reached 60.4%. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA, rpsA, and panD mutations showed that transmission of PZA-R isolates played a significant role in the formation of PZA-R TB. Ninety-eight mutation patterns were observed in the pncA among 180 PZA-R isolates, and seventy-one (72.4%) were point mutations. Twenty-four of these mutations are new, including 2 base substitutions (V93G and T153S) and 22 nucleotide deletions or insertions. The W119C was found in PZA-S isolates, on the other hand, F94L and V155A mutations were found in both PZA resistant and susceptible isolates with positive PZase activity, indicating that they were not associated with PZA resistance. This is not entirely in line with the WHO catalogue. Ten novel rpsA mutations were found in 10 PZA-R isolates, which all combined with mutations in pncA. Thus, it is unpredictable whether these mutations in rpsA can impact PZA resistance. No panD mutation was found in all PZA-R isolates.Conclusion: DNA sequencing of pncA and PZase activity testing have great potential in predicting PZA resistance.Keywords: tuberculosis, pyrazinamide, transmission, pncA mutations, rpsA mutations, panD mutations, China

Yi-Can Yang,1 Qiong Tang,1 Li-Juan Yan,1 Shi-Bin Zhang,2 Xiao-Min Ye,1 Dai Gong,1 Li Zou,1 Xiang-Lan Wen1 1Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou City, Hunan Province, 412007, People’s Republic of China; 2Department of Pediatrics, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou City, Hunan Province, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 of Changjiang South Road, Tianyuan District, Zhuzhou City, Hunan Province, 412007, People’s Republic of China, Tel/Fax +8673128561905, Email wenxianglianwxl@126.comBackground: Floating-Harbor syndrome (FHS) is a rare autosomal dominant inherited disease characterized primarily by short stature, delayed language development, and typical facial features. There are currently few case reports, diagnoses and treatments for these syndromes at home and abroad.Case Description: This study reports a case of a boy with “growth and language development delay” as the predominant clinical manifestation. FHS was clinically diagnosed based on his growth hormone (GH) deficiency, significant bone age delay, left testicular hydrocele, and the whole exon gene in peripheral blood, which indicated heterozygous mutation of SRCAP gene. Following the treatment with recombinant human GH (rhGH), the child exhibited height increase benefits, and his articulation improved after language therapy.Conclusion: Genetic testing facilitates early detection, diagnosis, and treatment of the FHS. Additionally, treatment with rhGH effectively increases the height of these children, and language rehabilitation is especially important for their language development.Keywords: Floating-Harbor syndrome, language development, growth and development, rhGH, language rehabilitation

Qiong Tang, Dai Gong, Xiao-Min Ye, Jun-Ru Xu, Yi-Can Yang, Li-Juan Yan, Li Zou, Xiang-Lan Wen Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 of Changjiang South Road, Tianyuan District, Zhuzhou City, Hunan Province, 412007, People’s Republic of China, Tel +86 13873317331, Email wenxianglianwxl@126.comAbstract: Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous syndrome (CFCS). Although CFCS is considered rare, approximately 300 cases have been documented in the literature. In this report, we discuss a patient diagnosed with CFCS without the typical heart malformations but with craniofacial features, skin abnormalities, intellectual disability, and short stature. Genetic testing revealed the presence of three potentially harmful variants: one in the MAP2K1 gene and two in the ATP2B3 and CDC42BPB genes, the significance of which is currently not yet found. Our findings in this case report suggest that the clinical symptoms of CFCS may be atypical, thereby expanding our understanding of the symptom spectrum of the disease. Simultaneously, the link between the clinical symptoms of the patient and the two unknown pathogenic variants has not been established. This case report supplements existing clinical reference material by providing valuable insights into the specific scenario.Keywords: cardiofaciocutaneous syndrome, gene detection, intellectual disability, neurodevelopmental syndrome, short stature, spinocerebellar ataxia

Dai Gong, Qiong Tang, Li-Juan Yan, Xiao-Min Ye, Yi-Can Yang, Li Zou, Qing Ji, Xiang-Lan Wen Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, Hunan, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 Changjiang Road, Tianyuan District, Zhuzhou, Hunan, 412007, People’s Republic of China, Tel/Fax +86 13873317331, Email wenxianglianwxl@126.comBackground: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air.Case Description: We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary.Conclusion: The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.Keywords: gene test, primary ciliary dyskinesia, reduced ciliary clearance function, short stature

Omar Moussa,1 Tahvi Frank,2 Ives A Valenzuela,1 Joah Aliancy,1 Dan Gong,3 Joaquin O De Rojas,4 Lora R Dagi Glass,1 Bryan J Winn,5 George A Cioffi,1 Royce WS Chen1 1Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY, USA; 2Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; 3Department of Ophthalmology, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; 4Center for Sight, Sarasota, FL, USA; 5Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USACorrespondence: Royce WS Chen, Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, 635 W. 165th St, New York, NY, 10032, USA, Tel +1 212-305-9535, Email rc2631@cumc.columbia.eduPurpose: To evaluate efficacy of a novel risk stratification system in minimizing resident surgical complications and to evaluate whether the system could be used to safely introduce cataract surgery to earlier levels of training.Materials and Methods: This is a retrospective cross-sectional study on 530 non-consecutive cataract cases performed by residents at Columbia University. Risk scores, preoperative best corrected visual acuity (BCVA), intraoperative complications, postoperative day 1 (POD1), and month 1 (POM1) exam findings were tabulated. The relationship between risk scores and POD1 and POM1 BCVA was modeled using linear regression. The relationship between risk scores and complication rates was modeled using logistic regression. Logistic regression was used to model the rates of complications across different levels of training. Rates of complications were compared between diabetic versus non-diabetic patients using t-tests.Results: Risk scores did not have significant association with intraoperative complications. Risk scores were predictive of corneal edema (OR = 1.36, p = 0.0032) and having any POM1 complication (OR = 1.20, p = 0.034). Risk scores were predictive of POD1 (β = 0.13, p < 0.0001) and POM1 (β = 0.057, p = 0.00048) visual acuity. There was no significant association between level of training and rates of intraoperative (p = 0.9) or postoperative complications (p = 0.06). Rates of intraoperative complication trended higher among diabetic patients but was not statistically significant (p = 0.2).Conclusion: Higher risk scores were predictive of prolonged corneal edema but not risk of intraoperative complications. Our risk stratification system allowed us to safely introduce earlier phacoemulsification surgery.Keywords: cataract, cataract risk stratification, resident phacoemulsification surgery

Fei Peng,1 Jing Liu,1,2 Yujun Zhang,1,2 Guoyan Zhao,1,2 Deying Gong,1,2 Liu He,1,2 Wensheng Zhang,1,2 Feng Qiu1,2 1Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Feng Qiu; Wensheng Zhang, Email fengqiu@scu.edu.cn; zhang_ws@scu.edu.cnIntroduction: Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide.Methods: Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect.Results: Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which could be mineralized to form drug/peptide nanocrystals by adjusting the pH. Under physiological condition, the nanocrystals could release free ropivacaine slowly. As evaluated in rodent models, the anesthetic and analgesic effects of this formulation were significantly extended without causing toxicity.Conclusion: Based on the interaction between ropivacaine and Q11, a controllable biomineralization process could be induced to obtain homogeneous nanocrystals, which could be used as an injectable long-acting analgesic formulation. This crystallization strategy utilizing the peptide-drug interaction also provided a promising pathway to fabricate long-acting formulations for many other small molecular drugs.Keywords: self-assembling peptide, nanocrystal, local anesthetics, π-π stacking, slow release, long-acting analgesia

Qiyun Jiang,1,2 Dan Gong,1,2 Huiqi Li,3 Donglan Zhang,4 Suzhen Hu,5 Qinghua Xia,6 Hong Yuan,7 Peng Zhou,6 Yiying Zhang,7 Xing Liu,8 Mei Sun,1,2 Jun Lv,1,2 Chengyue Li1,2 1Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Institute of Health Development Strategies, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, GA, USA; 5Department of Medical Affairs, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 6Department of Chronic Disease Prevention and Control, Changning District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Department of Chronic Disease Prevention and Control, Jiading District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 8Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Chengyue Li; Jun Lv, Department of Health Policy and Management, School of Public Health, Fudan University, P.O. Box 177, 130 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-33561022 ; +86-21-33563953, Fax +86-21-33563380, Email lichengyue@fudan.edu.cn; lujun@shmu.edu.cnPurpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797– 0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.Keywords: Eastern China, high-risk population, hypertension, risk scoring method, screening tool

Jing Liu,1,2 Fei Peng,1,2 Yi Kang,1,2 Deying Gong,1,2 Jing Fan,1,2 Wensheng Zhang,1,2 Feng Qiu1,2 1Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Feng Qiu; Wensheng Zhang Email fengqiu@scu.edu.cn; zhang_ws@scu.edu.cnPurpose: Typical hydrophobic amino acids (HAAs) are important motifs for self-assembling peptides (SAPs), but they lead to low water-solubility or compact packing of peptides, limiting their capacity for encapsulating hydrophobic drugs. As an alternative, we designed a peptide GQY based on atypical HAAs, which could encapsulate hydrophobic drugs more efficiently. Although hydrophobic general anesthetics (GAs) have been formulated as lipid emulsions, their lipid-free formulations have been pursued because of some side effects inherent to lipids. Using GAs as targets, potential application of GQY as a carrier for hydrophobic drugs was evaluated.Methods: Thioflavin-T (ThT) binding test, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to examine the self-assembling ability of GQY. Pyrene and 8-Anilino-1-naphthalenesulfonic acid (ANS) were used to confirm formation of hydrophobic domain in GQY nanoparticles. Using pyrene as a model, GQY’s capacity to encapsulate hydrophobic drugs was evaluated. GAs including propofol, etomidate and ET26 were encapsulated by GQY. Loss of righting reflex (LORR) test was conducted to assess the anesthetic efficacy of these lipid-free formulations. Paw-licking test was used to evaluate pain-on-injection of propofol-GQY (PROP-GQY) formulation. Hemolytic and cytotoxicity assay were used to evaluate biocompatibility of GQY.Results: Stable nanoparticles containing plenty of hydrophobic cavities could be formed by GQY, which could encapsulate hydrophobic drugs at very high concentration and form stable suspensions. Propofol, etomidate and ET26 formulated by GQY showed anesthetic efficacy comparable to their currently available formulations. Unlike clinic lipid emulsion, PROP-GQY formulation did not cause pain-on-injection in rats. Neither obvious cytotoxicity nor hemolytic activity of GQY was observed.Conclusion: GQY could encapsulate GAs to obtain stable and effective formulations. As a lipid-free carrier, GQY exhibited considerable biocompatibility and other side benefits such as reducing pain-on-injection. More SAPs based on atypical HAAs could be designed as promising carriers for hydrophobic drugs.Keywords: self-assembling peptides, nanoparticles, hydrophobic drugs, lipid-free formulations, general anesthetics

Debao Li,1,* Keyang Li,2,* Hongliang Dong,2 Dongmei Ren,1 Dandan Gong,2 Fuguo Jiang,1 Chunhua Shi,1 Junmin Li,1 Qi Zhang,3 Wenjuan Yan,3 Yi Li3 1Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi LiDepartment of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7#, Jinshui District, Zhengzhou, 450003, Henan, People’s Republic of ChinaTel +86 15225061830; +86 15939039006Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a serious problem worldwide. Herein, we describe the evolution of ceftazidime–avibactam (CZA) resistance by sequencing clinical isolates from a patient with CRKP infection undergoing CZA treatment.Patients and Methods: In this study, six CRKP strains were isolated from sputum and blood samples of a patient with CRKP infection after intracerebral hemorrhage. Two strains were selected for whole-genome analysis.Results: Drug susceptibility testing showed that the MIC of CZA for CRKP strains isolated after 6 days of CZA treatment was 64-fold higher than that for three CRKP strains isolated before CZA treatment (4 vs > 256 μg/mL), whereas the MIC of imipenem and meropenem was 128-fold (> 32 vs 0.25 μg/mL) and 16-fold (> 32 vs 2 μg/mL) lower relatively, respectively. Multilocus sequence typing showed that all six CRKP strains isolated from the patient were ST11 and pulsed-field gel electrophoresis confirmed that they were of the same clone. Two strains were selected for whole-genome analysis. The aspartic acid residue at position 179 in the Ω loop was replaced by a tyrosine residue in the resistant strain, and the plasmid carried a blaKPC-2 to blaKPC-33 mutation. The results of the modified carbapenem inactivation method and the carbapenemase inhibitor enhancement and colloidal gold enzyme immunochromatographic assays for blaKPC-33 were negative.Conclusion: This is the first report from Henan to show that treatment with CZA for 6 days can cause mutations and change the phenotype from CZA sensitive to resistant. Therefore, routine testing for drug susceptibility and carbapenemase phenotypes should be conducted during treatment with CZA, and genotype determination is essential.Keywords: ceftazidime–avibactam, drug resistance, carbapenem-resistant Klebsiella pneumoniae, K. pneumoniae carbapenemase-2, ST11

Microstructural evolution and compressive properties of two-phase Nb-Fe binary alloys based on the C14 Laves phase NbFe2 were characterized at both the hypo- and hypereutectic compositions. The experimental results indicated that the microstructures of the two alloys consisted of fully eutectics containing Fe and NbFe2 phases at the bottom of the ingots corresponding to the largest solidification rates. With the decrease of solidification rate, the microstructures developed into primary Fe (NbFe2) dendrites plus eutectics in the middle and top parts of the ingots. The microstructural evolutions along the axis of the ingots were analyzed by considering the competitive growth between the primary phase and eutectic as well as using microstructure selection models based on the maximum interface temperature criterion. Furthermore, the compressive properties of the two alloys were measured and the enhancements were explained in terms of the second Fe phase and halo toughening mechanisms.

Type 2 diabetes is caused by chronic insulin resistance and progressive decline in beta-cell function. Optimal beta-cell function and mass is essential for glucose homeostasis and beta-cell impairment leads to the development of diabetes. Elevated levels of circulating fatty acids (FAs) and disturbances in lipid metabolism regulation are associated with obesity, and they are major factors influencing the increase in the incidence of type 2 diabetes. Chronic free FA (FFA) treatment induces insulin resistance and beta-cell dysfunction; therefore, reduction of elevated plasma FFA levels might be an important therapeutic target in obesity and type 2 diabetes. Lipid signals via receptors, and intracellular mechanisms are involved in FFA-induced apoptosis. In this paper, we discuss lipid actions in beta cells, including effects on metabolic pathways and stress responses, to help further understand the molecular mechanisms of lipotoxicity-induced type 2 diabetes.

Dianrong Gong,1 Haiyan Yu,1 Weihua Wang,2 Haixin Yang,1 Fabin Han1,21Department of Neurology, 2Centre for Stem Cells and Regenerative Medicine, Liaocheng People's Hospital, The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of ChinaAbstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs) to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI). The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy.Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE

This paper presents the design and simulation results of a gigabit transceiver Application Specific Integrated Circuit (ASIC) called GBCR for the ATLAS Inner Tracker (ITk) Pixel detector readout upgrade. GBCR has four upstream receiver channels and a downstream transmitter channel. Each upstream channel operates at 5.12 Gbps, while the downstream channel operates at 2.56 Gbps. In each upstream channel, GBCR equalizes a signal received through a 5-meter 34-American Wire Gauge (AWG) twin-axial cable, retimes the data with a recovered clock, and drives an optical transmitter. In the downstream channel, GBCR receives the data from an optical receiver and drives the same type of cable as the upstream channels. The output jitter of an upstream channel is 26.5 ps and the jitter of the downstream channel after the cable is 33.5 ps. Each upstream channel consumes 78 mW and each downstream channel consumes 27 mW. Simulation results of the upstream test channel suggest that a significant jitter reduction could be achieved with minimally increased power consumption by using a Feed Forward Equalizer (FFE) + Decision Feedback Equalization (DFE) in addition to the linear equalization of the baseline channel. GBCR is designed in a 65-nm CMOS technology.

Over the past decade, as consumers have gradually adapted to electric vehicles, the production and sales of electric vehicles have grown in tandem, and the deployment of charging facilities has increased dramatically. However, along with the rapid development in scale, charging facilities face problems such as low utilisation during off-peak hours and excessive congestion during peak hours. Therefore, research on the spatial and temporal distribution of charging station loads is of great value. In this context, this study focuses on the spatio-temporal distribution characteristics of charging station loads, especially when analysing the spatial distribution characteristics. This study defines the spatially dependent characteristics of short and long distance. In order to be closer to real charging scenarios, this study considers the influence of road network information and point-of-interest data on the spatial distribution of loads. The spatial and temporal variations of loads and influencing factors are considered more comprehensively and richly, and the spatial characteristics are delineated in detail. [ABSTRACT FROM AUTHOR]

The adoption of electric vehicles (EVs) represents a pivotal shift towards sustainable mobility, yet the challenge of efficient charging station recommendations persists, influencing user convenience and EV uptake. This study introduces a novel approach utilizing Q-learning for simulating EV charging station recommendations, aiming to optimize the matching process between EVs and charging infrastructure. By integrating Markov decision processes with Q-learning algorithms, we dynamically adapt recommendations to user behaviours and preferences, significantly enhancing recommendation accuracy and personalization. The methodology involves constructing a simulation environment to model EV charging behaviour, evaluating the performance of the Q-learning based recommendation system under various scenarios. Results demonstrate the effectiveness of this approach in identifying optimal charging strategies, thus contributing to improved user satisfaction and charging station utilization. The findings underscore the importance of innovative technological integration for addressing the complexities of sustainable urban mobility. [ABSTRACT FROM AUTHOR]

Ride-hailing services have transformed urban transportation through convenience yet introduced new complexities around efficiency and traffic management. This study investigates the dual-queuing problem in ride-hailing from the driver perspective using a multi-agent simulation approach. The focus is dissecting the dynamics between driver search times and passenger wait times, which critically influence operational efficiency especially during peak demand. Exploring these interactions aims to uncover insights that could improve service efficiency and customer satisfaction. Addressing such ride-hail- ing challenges is vital not just for individual providers but also for advancing sustainable mobility across rapidly growing metropolitan regions. Enhanced efficiency connects to broader urban development narratives around livability, accessibility, and responsible mobility ecosystems. [ABSTRACT FROM AUTHOR]