novoPathFinder: a webserver of designing novel-pathway with integrating GEM-model

To increase the number of value-added chemicals that can be produced by metabolic engineering and synthetic biology, constructing metabolic space with novel reactions/pathways is crucial. However, with the large number of reactions that existed in the metabolic space and complicated metabolisms within hosts, identifying novel pathways linking two molecules or heterologous pathways when engineering a host to produce a target molecule is an arduous task. Hence, we built a user-friendly web server, novoPathFinder, which has several features: (i) enumerate novel pathways between two specified molecules without considering hosts; (ii) construct heterologous pathways with known or putative reactions for producing target molecule within Escherichia coli or yeast without giving precursor; (iii) estimate novel pathways with considering several categories, including enzyme promiscuity, Synthetic Complex Score (SCScore) and LD50 of intermediates, overall stoichiometric conversions, pathway length, theoretical yields and thermodynamic feasibility. According to the results, novoPathFinder is more capable to recover experimentally validated pathways when comparing other rule-based web server tools. Besides, more efficient pathways with novel reactions could also be retrieved for further experimental exploration. novoPathFinder is available at http://design.rxnfinder.org/novopathfinder/

The impact of climate change on infectious disease transmission: perceptions of CDC health professionals in Shanxi Province, China

There have been increasing concerns about the challenge of emerging and re-emerging infectious diseases due to climate change, especially in developing countries including China. Health professionals play a significant role in the battle to control and prevent infectious diseases. This study therefore aims to investigate the perceptions and attitudes of health professionals at the Centers for Disease Control and Prevention (CDC) in different levels in China, and to consider adaptation measures to deal with the challenge of climate change. In 2013, a cross-sectional questionnaire survey was undertaken among 314 staff in CDCs in Shanxi Province, China, whose routine work involves disease control and prevention. Data were analyzed using descriptive methods and logistic regression. A majority of the CDC staff were aware of the health risks from climate change, especially its impacts on infectious disease transmission in their jurisdictions, and believed climate change might bring about both temporal and spatial change in transmission patterns. It was thought that adaptation measures should be established including: strengthening/improving currently existing disease surveillance systems and vector monitoring; building CDC capacity in terms of infrastructure and in-house health professional training; development and refinement of relevant legislation, policies and guidelines; better coordination among various government departments; the involvement of the community in infectious disease interventions; and collaborative research with other institutions. This study provides a snapshot of the understanding of CDC staff regarding climate change risks relevant to infectious diseases and adaptation in China. Results may help inform future efforts to develop adaptation measures to minimize infectious disease risks due to climate change.Junni Wei, Alana Hansen, Ying Zhang, Hong Li, Qiyong Liu, Yehuan Sun, Shulian Xue, Shufang Zhao, Peng B

Sustainable supply chain management towards disruption and organizational ambidexterity:A data driven analysis

Balancing sustainability and disruption of supply chains requires organizational ambidexterity. Sustainable supply chains prioritize efficiency and economies of scale and may not have sufficient redundancy to withstand disruptive events. There is a developing body of literature that attempts to reconcile these two aspects. This study gives a data-driven literature review of sustainable supply chain management trends toward ambidexterity and disruption. The critical review reveals temporal trends and geographic distribution of literature. A hybrid of data-driven analysis approach based on content and bibliometric analyses, fuzzy Delphi method, entropy weight method, and fuzzy decision-making trial and evaluation laboratory is used on 273 keywords and 22 indicators obtained based on the experts’ evaluation. The most important indicators are identified as supply chain agility, supply chain coordination, supply chain finance, supply chain flexibility, supply chain resilience, and sustainability. The regions show different tendencies compared with others. Asia and Oceania, Latin America and the Caribbean, and Africa are the regions needs improvement, while Europe and North America show distinct apprehensions on supply chain network design. The main contribution of this review is the identification of the knowledge frontier, which then leads to a discussion of prospects for future studies and practical industry implementation

The effect of meteorological variables on the transmission of hand, foot and mouth disease in four major cities of Shanxi province, China: a time series data analysis (2009-2013)

Increased incidence of hand, foot and mouth disease (HFMD) has been recognized as a critical challenge to communicable disease control and public health response. This study aimed to quantify the association between climate variation and notified cases of HFMD in selected cities of Shanxi Province, and to provide evidence for disease control and prevention. Meteorological variables and HFMD cases data in 4 major cities (Datong, Taiyuan, Changzhi and Yuncheng) of Shanxi province, China, were obtained from the China Meteorology Administration and China CDC respectively over the period 1 January 2009 to 31 December 2013. Correlations analyses and Seasonal Autoregressive Integrated Moving Average (SARIMA) models were used to identify and quantify the relationship between the meteorological variables and HFMD. HFMD incidence varied seasonally with the majority of cases in the 4 cities occurring from May to July. Temperatures could play important roles in the incidence of HFMD in these regions. The SARIMA models indicate that a 1° C rise in average, maximum and minimum temperatures may lead to a similar relative increase in the number of cases in the 4 cities. The lag times for the effects of temperatures were identified in Taiyuan, Changzhi and Yuncheng. The numbers of cases were positively associated with average and minimum temperatures at a lag of 1 week in Taiyuan, Changzhi and Yuncheng, and with maximum temperature at a lag of 2 weeks in Yuncheng. Positive association between the temperature and HFMD has been identified from the 4 cities in Shanxi Province, although the role of weather variables on the transmission of HFMD varied in the 4 cities. Relevant prevention measures and public health action are required to reduce future risks of climate change with consideration of local climatic conditions.Junni Wei, Alana Hansen, Qiyong Liu, Yehuan Sun, Phil Weinstein, Peng B

Expression and clinical significance of PD-1, PD-L1 and tumor infiltrating lymphocytes in neuroblastoma

Objective To investigate the expression of programmed cell death protein 1(PD-1), programmed cell death 1 ligand 1 (PD-L1) and tumor infiltrates lymphocytes (TIL) density in neuroblastoma and the relationship between them and the clinicopathological features of patients. Methods The postoperative tumor tissues of 58 patients with neuroblastoma who underwent surgical resection in Shanxi Children ‘s Hospital from January 2000 to June 2022 were selected, and the expression of PD-1 in tumor lymphocytes and PD-L1 in tumor cells were detected by immunohistochemical method. T lymphocyte density of CD3+, CD4+ and CD8+ was detected. The expression of PD-1 and PD-L1 and the relationship between T lymphocyte density of different subgroups and clinicopathological characteristics were analyzed. Results The positive expression rates of PD-1 and PD-L1 protein were 44.8% and 43.1%, respectively. There were significant differences in the expression of PD-L1 in INSS stage, INRGSS stage, pathological type and differentiation type (P<0.05). PD-1 expression was significantly different in different tumor location, INSS stage and INRGSS stage (P<0.05). PD-1 was correlated with PD-L1 expression (r=0.318, P=0.011). The density of tumor infiltrating T cells was significantly different in different INSS stage and INRGSS stage (P<0.05). The expression of CD3+T cells around the nest, CD3+T cells in the nest and CD8+T cells around the nest were correlated with the expression of PD-1 (r=0.265, 0.287, 0.309, P＜0.05.) Conclusion High expression of PD-L1 in neuroblastoma predicts worse prognosis, and tumor-infiltrating T lymphocytes may be involved in the regulation of PD-1 expression. Immunotherapy targeting PD-1/PD-L1 signaling pathway is expected to be a potential therapeutic target for neuroblastoma

Infections associated with CAR‐T cell therapy in patients with relapsed refractory multiple myeloma: Risks and prevention strategies

Abstract Background Chimeric antigen receptor T (CAR‐T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment‐related toxicities, particularly infections, pose a significant challenge to patient safety. Methods This review synthesizes current knowledge on the mechanisms underlying post‐CAR‐T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment‐induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome. Results The review identifies that patients receiving CAR‐T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome. Conclusion To enhance the infection control post‐CAR‐T therapy, this review proposes preventive strategies tailored to the early and long‐term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment

A Fast and Accurate Self-Healing Scheme for Intelligent Distribution Networks Using Mixed Integer Linear Programming

Fast and accurate self-healing after faults is an important way to improve the reliability of distribution networks. To improve the self-healing speed and accuracy of distribution networks, this paper proposes a fast and accurate self-healing scheme for distribution networks using mixed integer linear programming. Firstly, this method constructs a centralized 5G communication network architecture, which can effectively reduce the communication delay during the self-healing process. Secondly, the principle of logical algebraic transformation is utilized to linearize the switch function in the fault location model, thereby achieving equivalent transformation of the fault location model. Thirdly, using the polyhedral approximation method, the mixed integer second-order cone programming of the power supply recovery model is transformed into a mixed integer linear programming. The proposed method was validated by distribution network systems with different nodes in MATLAB/Simulink, and the results showed that the proposed method significantly improved self-healing speed and accuracy

Notified weekly cases of hand-foot-mouth disease (HFMD) and autocorrelation function (ACF) and Partial ACF (PACF) plot of original number of HFMD cases in 4 cities, Shanxi, 2009–2013.

<p>A and E: the number of HFMD cases, ACF and PACF plots of Datong. B and F: the number of HFMD cases, ACF and PACF plots of Taiyuan. C and G: the number of HFMD cases, ACF and PACF plots of Changzhi. D and H: the number of HFMD cases, ACF and PACF plots of Yuncheng.</p

Prediction of the number of HFMD cases on the basis of the model without and with weather variables.

<p>A, B, C, D: Datong, Taiyuan, Changzhi and Yuncheng, respectively.</p