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Tianrui Zhang,1,* Sha Fu,1,* Xiaofeng Cao,2 Yangjingyi Xia,1 Manyan Hu,1 Qinghua Feng,1 Yujun Cong,1 Yuan Zhu,1 Xiaogang Tang,1 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Neurology, Jiangyan Hospital of Chinese Medicine, Taizhou, Jiangsu, 225500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minghua Wu; Xiaogang Tang, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Tel +8613951786719, Email yfy0069@njucm.edu.cn; zhongyiTXG@163.comPurpose: According to many previous studies, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and hypersensitive C-reactive protein (CRP) are commonly used as important indicators to assess the prognosis of intravenous thrombolysis in AIS patients. Based on this, we used two novel biomarkers C-NLR (CRP/neutrophil-to-lymphocyte ratio) and C-LMR (CRP×lymphocyte-to-monocyte ratio) to investigate their correlation with 90-day outcomes in AIS patients after intravenous thrombolysis.Patients and Methods: A total of 204 AIS patients who received intravenous thrombolysis at the Stroke Center of Jiangsu Province Hospital of Chinese Medicine from January 2021 to December 2022 were retrospectively included. All patients were followed up 90 days after thrombolysis to assess their prognosis. Patients with a modified Rankin scale score (mRS) of 3– 6 were included in the unfavorable outcome group, and those with a score of 0– 2 were included in the favorable outcome group. Logistic regression analysis, receiver operating characteristic (ROC) curve, and Kaplan–Meier survival curve were used to investigate the association between C-NLR, C-LMR, and 90-day prognosis in AIS patients treated with early intravenous thrombolysis.Results: C-NLR (OR=1.586, 95% CI=1.098~2.291, P=0.014) and C-LMR (OR=1.099, 95% CI=1.025~1.179, P=0.008) were independent risk factors for 90-day prognosis of AIS patients treated with early intravenous thrombolysis. The higher C-NLR and C-LMR were associated with unfavorable prognosis.Conclusion: C-NLR and C-LMR can be used as biomarkers to predict prognosis of AIS patients treated with early intravenous thrombolysis.Keywords: modified rankin scale, reperfusion therapy, inflammatory reaction, cerebral vascular disease, clinical prognosis

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern. The development of vaccines with high immunogenicity and safety is crucial for controlling the global COVID-19 pandemic and preventing further illness and fatalities. Here, we report the development of a SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the spike (S) protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG and neutralizing antibodies in three animal models: BALB/c mouse, Syrian hamster, and a non-human primate (Macaca leonina). In addition, a viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. Nanocovax did not induce any adverse effects in mice (Mus musculus var. albino) and rats (Rattus norvegicus). These preclinical results indicate that Nanocovax is safe and effective.

Remobilization is an important mechanism of resource conservation in plants. However, our understanding of whether the responses of resource remobilization to global warming differ between deciduous and evergreen trees remains unclear. We assessed resource remobilization from leaves to 1-year-old shoots in a deciduous (Betula ermanii) and an evergreen (Quercus aquifolioides) species along elevational gradients (i.e., temperature gradient) at the end of growing season. We aimed to test the hypotheses that the reallocation rate increased with increasing elevation and that more resources were reallocated from leaves to storage tissues in deciduous species than in evergreen species. We analyzed the concentrations of non-structural carbohydrates (NSC), nitrogen (N) and phosphorus (P), and compared the differences in remobilization efficiency of NSC, N, and P between leaves and shoots within each species and between the two species along the elevational gradients. Due to the different strategies of evergreen and deciduous species in nutrients use, the deciduous species had higher N and P remobilization rate, but lower remobilization rate of sugars, starch, and NSC than the evergreen species at the end of growing season. The remobilization rate of NSC, N, and P was significantly higher in trees at their upper limits compared to lower elevations. Our results suggest that trees reallocate resources from leaves to storage tissues before leaf senescence or at the end of growing season, to increase the resource use efficiency and to adapt to the harsh alpine environments. These results contribute to better understanding of the alpine treeline phenomenon in a changing world.

Chao Liu,1,2 Bing Sun,2 Bin Xu,1 Xiangying Meng,2 Lan Li,1 Yang Cong,2 Jiannan Liu,2 Qian Wang,2 Liang Xuan,2 Qibin Song,1 Shikai Wu2 1Cancer Center, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People’s Republic of China Introduction: Programmed cell death protein 1 (PD-1), an immune checkpoint molecule, has recently been recognized as a predictive and prognostic biomarker in several malignant tumors, but its diagnostic value remains largely unknown. We aimed to investigate the differential diagnostic efficiency of PD-1 and other immune molecules and propose a panel of immune molecules combined with cancer antigen 15-3 (CA15-3) to distinguish breast cancer (BC) from benign breast disease (BBD).Patients and methods: Ninety-one eligible BC patients and 31 BBD patients were enrolled. Pretreatment peripheral blood was collected and tested for mRNA expression of PD-1, cytotoxic T lymphocyte antigen 4, forkhead box P3, transforming growth factor beta, interleukin-10 (IL-10), IL-2 receptor alpha (IL-2Rα), and cluster of differentiation 28 by quantitative reverse transcription PCR.Results: The diagnostic areas under curve (AUCs) of PD-1, IL-2Rα, and IL-10 for BC–BBD discrimination were 0.764, 0.758, and 0.743, respectively. The diagnostic efficiencies of these three parameters in distinguishing early-stage or advanced BC from BBD were consistent with a role in BC–BBD discrimination. A panel of PD-1 + IL-10 + IL-2Rα + CA15-3 showed the highest AUC (0.862), with a sensitivity of 0.933 and a specificity of 0.724, for BC–BBD discrimination. In addition, for early-stage BC discrimination, this panel also had the highest AUC (0.811), with a sensitivity of 0.933 and a specificity of 0.614, while for advanced BC discrimination, a panel of PD-1 + IL-10 + CA15-3 exhibited the highest AUC (0.896), with a sensitivity of 0.933 and a specificity of 0.783.Conclusion: These data indicate that the panel containing PD-1, IL-2Rα, IL-10, and CA15-3 can effectively discriminate BC from BBD with a high efficiency. After further confirmation, it could be used to complement conventional imaging modalities, especially in discriminating early-stage BC from BBD. Keywords: breast cancer, immune checkpoint, PD-1, CTLA-4, IL-2Rα, diagnosis, biomarker

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.