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Purpose: Accumulating evidence has elucidated that the interaction between cancer cells and M2 macrophages plays an important role in the tumorigenesis of hepatocellular carcinoma (HCC). However, the mechanism connecting tumor-derived exosomes, M2 polarization of macrophages, and liver metastasis remain unclear. Therefore, it is necessary to explore their influence on the tumor microenvironment of HCC., Methods: Transmission electron microscopy, nanometer particle testing, and special biomarker analysis were utilized to characterize exosomes, while the differential expression of microRNAs was evaluated using high-throughput sequencing technology. The functions of miR-200b-3p exosomes were confirmed using in vitro and in vivo assays. The interactions between microRNAs and ZEB1 as well as cancer cells and macrophages were measured using RNA pull-down and luciferase gene reporter assays., Results: Using in silico analysis, we identified high levels of miR-200b-3p exosome expression in patients with HCC, particularly with relapsed HCC. We demonstrated that HCC cell-derived miR-200b-3p exosomes were internalized by M0 macrophages and induced M2 polarization by downregulating ZEB1 and upregulating interleukin-4. As a result, the JAK/STAT signaling pathway was activated in M2 macrophages, leading to increased PIM1 and VEGFα expression. These cell factors accelerated the proliferation and metastasis of HCC, resulting in a feedback loop between HCC cells and M2 macrophages., Conclusion: The study illustrates that HCC cell-derived miR-200b-3p exosomes facilitate the proliferation and polarization of macrophages by modulating cytokine secretion and the JAK/STAT signaling pathway, leading to the metastasis of HCC. These findings demonstrate the existence of a novel feedback loop between cancer cells and immune cells in the tumor microenvironment, presenting a new concept in cancer research., (© 2023. Asian Pacific Association for the Study of the Liver.)

Background: Hepatocellular carcinoma (HCC) cell-derived exosomal LncRNA SNHG16 is highly expressed and associated with poor overall survival of patients. Telocytes (TCs), as novel interstitial cells, have been reported to promote HCC metastasis. Therefore, in our study, we investigated whether a molecular interaction occurred between exosomal LncSNHG16 and TCs in the tumor microenvironment., Methods: LncSNHG16 expression in HCC tissues and cell lines was measured, and bioinformatics analysis was performed. Exosomes were isolated and purified from HCC cells with LncSNHG16 overexpression/knockdown vectors and cocultured with TCs. Then, markers of the LncSNHG16/miR-942-3p/MMP9 axis were tested in TCs. Transwell assays and cell wound healing assays were designed to examine the invasion and migration of HCC cells after coincubation with TCs. RNA immunoprecipitation (RIP) assays and dual-luciferase gene reporter assays were performed to verify the binding effect of LncSNHG16, miR-942-3p, and MMP9 mRNA. In vivo, experimental animal models were established to confirm the effect of exosomal LncSNHG16-induced MMP9 expression on HCC metastasis., Results: Exosomal LncSNHG16 was phagocytized by TCs and downregulated miR-942-3p, which induced targeted MMP9 upregulation, and it had specific binding sites with miR-942-3p in TCs to facilitate the migration of HCC cells in vitro and in vivo. Exosomal LncSNHG16 was found to act as a competing endogenous RNA of the miR-942-3p/MMP9 axis in TCs., Conclusion: Tumour-derived exosomal LncSNHG16 modulates MMP9 via competitively binding to miR-942-3p in TCs, thus promoting the metastasis of HCC., (© 2022. Springer Nature Switzerland AG.)

The burden of disease caused by ambient high temperature has become a public health concern, but the associations between high temperature and hand, foot, and mouth disease (HFMD) remain indistinct. We used distributed lag non-linear model (DLNM) to estimate the burden of disease attribute to high temperature, adjusting for long-term trend and weather confounders. Total 18,167,455 cases were reported in 31 Chinese provinces, the incidence of HFMD showed a gradually increasing trend from 2008 to 2017 in China. Minimum morbidity temperature (MMT) was mainly concentrated at 17 to 23 °C in ≤ 5 years old group, 18 to 25 °C in 6 ~ 10 years old group and 19 to 27 °C in > 10 years old group. The greatest relative risk (RR) in age group ≤ 5 years old was 2.06 (95% CI: 1.85 ~ 2.30) in Heilongjiang, and the lowest RR was 1.02 (95% CI: 1.00 ~ 1.05) in Guangdong; the greatest RR in age group 6 ~ 10 years old was 2.24 (95% CI: 1.72 ~ 2.91) in Guizhou, and the lowest RR was 1.01 (95% CI: 0.97 ~ 1.12) in Tianjin; the greatest RR in the age group > 10 years old was 2.53 (95% CI: 1.66 ~ 3.87) in Heilongjiang, and the lowest RR was 1.02 (95% CI: 0.71 ~ 1.46) in Henan. We found the positive association between high temperature and HFMD in China., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Carbapenem-resistant Klebsiella pneumoniae are distributed worldwide. This study aimed to characterize a hypervirulent tigecycline-resistant and carbapenem-resistant Klebsiella pneumoniae strain, XJ-K2, collected from a patient's blood. We tested antimicrobial susceptibility, virulence, and whole-genome sequencing (WGS) on strain XJ-K2. WGS data were used to identify virulence and resistance genes and to perform multilocus sequence typing (MLST) and phylogenetic analysis. Three novel plasmids, including a pLVPK-like virulence plasmid (pXJ-K2-p1) and two multiple resistance plasmids (pXJ-K2-KPC-2 and pXJ-K2-p3), were discovered in strain XJ-K2. The IncFII(pCRY) plasmid pXJ-K2-p3 carried the dfrA14, sul2, qnrS1, bla LAP-2 , and tet(A) resistance genes. The IncFII(pHN7A8)/IncR plasmid pXJ-K2-KPC-2 also carried a range of resistance elements, containing rmtB, bla KPC-2 , bla TEM-1 , bla CTX-M-65 , and fosA3. MLST analysis revealed that strain XJ-K2 belonged to sequence type 11 (ST11). Seven complete phage sequences and many virulence genes were found in strain XJ-K2. Meanwhile, antimicrobial susceptibility tests and G. mellonella larval infection models confirmed the extensively drug resistance (XDR) and hypervirulence of KJ-K2. To our knowledge, this is the first observation and description of the ST11 hypervirulent tigecycline- and carbapenem-resistant K. pneumoniae strain co-carrying bla KPC-2 and the tet(A) in a patient's blood in China. Further investigation is needed to understand the resistance and virulence mechanisms of this significant hypervirulent tigecycline- and carbapenem-resistant strain., (© 2022. The Author(s).)

Purpose: The aim of the study was to evaluate the cognitive functions and seizure outcomes of patients with low-grade epilepsy-associated neuroepithelial tumors (LEATs)., Methods: We retrospectively reviewed the clinical data of patients who underwent preoperative neuropsychological evaluations and subsequent epilepsy surgery for LEATs. The neuropsychological results of full-scaled intelligence quotient (FSIQ) and full-scaled memory quotient (FSMQ) were analyzed, as well as the postoperative seizure outcomes., Results: Of the 138 patients included in the study, 59 patients (40.4%) were female and 47 (36.6%) patients were children. Preoperatively, 138 patients received FSIQ assessments and 30 patients (21.7%) had an intellectual deficit (FSIQ < 80 scores); 124 patients received FSMQ assessments and 32 patients (25.8%) had a memory deficit (FSMQ < 80 scores). Younger age at seizure onset (OR 0.93; P = 0.035) and discordant ictal electroencephalography (EEG) findings (OR 5.26; P = 0.001) were found to predict intellectual deficits, while abnormal hippocampus (OR 2.36; P = 0.051) as well as discordant ictal EEG findings (OR 4.03; P = 0.007) tended to cause memory deficits. During postoperative follow-up, 123 patients (90.7%) were followed up at least 12 months, and among them, 105 patients (85.4%) got seizure-free (Engel class I), while 18 patients (14.6%) were not (Engel class II-IV); longer duration of epilepsy (OR 1.01; P < 0.001) and discordant interictal EEG findings (OR 5.91; P = 0.005) were found to be related to poor seizure outcomes in patients with LEATs., Conclusion: Cognitive deficits commonly occur in patients with LEATs, especially in patients with early or childhood seizures. Early surgical intervention, however, could prevent most of patients from repeated seizure onsets and thus cognitive impairments., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The problem of algal bloom caused by eutrophication has attracted global attention. Many scholars have studied the problem associated with algae bloom, but few have carried out dynamic monitoring, instead focusing on the formation mechanism of cyanobacteria. For our study of the Taihu Lake in China, we used Moderate-Resolution Imaging Spectroradiometer (MODIS) and Landsat remote sensing image data from 2017 to establish a prediction model. First, we used MODIS data to retrieve the concentration of N, P, and chlorophyll a in water. Then, we applied the analytic hierarchy process (AHP) model to the inversion results to construct the diffusion potential index. Finally, we used C# to compile the cellular automata (CA) model. We found that the distribution of cyanobacteria predicted by our method was consistent with the algal bloom situation of Taihu Lake in 2017. The results showed that the method effectively predicts the dynamic transfer of cyanobacteria from outbreak to diffusion in a short period of time, which can help decision-makers monitor lake health., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this paper, phase space reconstruction from stereo-electroencephalography data of ten patients with focal epilepsy forms a series of graphs. Those obtained graphs reflect the transition characteristics of brain dynamical system from pre-seizure to seizure of epilepsy. Interestingly, it is found that the rank of Laplacian matrix of these graphs has a sharp decrease when a seizure is close to happen, which thus might be viewed as a new potential biomarker in epilepsy. In addition, the reliability of this method is numerically verified with a coupled mass neural model. In particular, our simulation suggests that this potential biomarker can play the roles of predictive effect or delayed awareness, depending on the bias current of the Gaussian noise. These results may give new insights into the seizure detection., Competing Interests: Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature 2021.)

Epilepsy involves a diverse group of abnormalities, including molecular and cellular disorders. These abnormalities prove to be associated with the changes in local excitability and synaptic dynamics. Correspondingly, the epileptic processes including onset, propagation and generalized seizure may be related with the alterations of excitability and synapse. In this paper, three regions, epileptogenic zone (EZ), propagation area and normal region, were defined and represented by neuronal population model with heterogeneous excitability, respectively. In order to describe the synaptic behavior that the strength was enhanced and maintained at a high level for a short term under a high frequency spike train, a novel activity-dependent short-term plasticity model was proposed. Bifurcation analysis showed that the presence of hyperexcitability could increase the seizure susceptibility of local area, leading to epileptic discharges first seen in the EZ. Meanwhile, recurrent epileptic activities might result in the transition of synaptic strength from weak state to high level, augmenting synaptic depolarizations in non-epileptic neurons as the experimental findings. Numerical simulation based on a full-connected weighted network could qualitatively demonstrate the epileptic process that the propagation area and normal region were successively recruited by the EZ. Furthermore, cross recurrence plot was used to explore the synchronization between neuronal populations, and the global synchronization index was introduced to measure the global synchronization. Results suggested that the synchronization between the EZ and other region was significantly enhanced with the occurrence of seizure. Interestingly, the desynchronization phenomenon was also observed during seizure initiation and propagation as reported before. Therefore, heterogeneous excitability and short-term plasticity are believed to play an important role in the epileptic process. This study may provide novel insights into the mechanism of epileptogenesis., Competing Interests: Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Springer Nature B.V. 2020.)

Suicide prevention has become a public health issue of great concern. Previous studies proved that ambient temperature had an impact on suicide death, but few studies focus on regional studies in large cities. We aimed to estimate the association between ambient temperature and suicide in 31 capital cities in China during 2008~2013. Distributed lag non-linear model was used to explore the relationship between ambient temperature and suicide, adjusting for long-term trend, seasonality, and humidity confounders. Multivariate meta-analysis was used to pool the city-specific estimates to explore the overall relative risk in China. High temperature had a significant impact on suicide death. The country-level relative risk of high temperature on suicide was 1.37 (95% CI, 0.96~2.57), and the RR was higher in male and age < 65-year-old group than that in female and age ≥ 65-year-old group. There has no consistent pattern of associations in city-level with sex and age. The high temperature has a greater impact on suicide in south region compared with north region. We found the positive association between ambient temperature and suicide in China.