CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it. METHODS: A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments. CCDC25 expression levels in tumor vs. normal tissues were quantified using Western blot and immunofluorescence studies. Cell proliferation and migration were analyzed using CCK8, EDU, Transwell assays, and wound healing assays. RNA sequencing was performed to elucidate the molecular pathways affected, followed by detailed protein-protein interaction studies and mouse xenograft models. RESULTS: CCDC25 was predominantly underexpressed in ccRCC tumors and associated with advanced clinical stages and poor prognosis. Overexpression of CCDC25 in renal cancer cell lines resulted in reduced proliferation and migration. RNA sequencing revealed significant alterations in the Hippo pathway. Overexpression of CCDC25 inhibited the expression of downstream Hippo pathway proteins ITGA3 and CCND1 and promoted YAP phosphorylation. Mechanistic studies showed that CCDC25 interacts with YAP and influences YAP phosphorylation through LATS1. In vivo, CCDC25 overexpression inhibited tumor growth and promoted apoptosis. CONCLUSION: CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.

Ketoglutaric acid can reprogram the immunophenotype of triple-negative breast cancer after radiotherapy and improve the therapeutic effect of anti-PD-L1.

BACKGROUND: Great progress has been made in applying immunotherapy to the clinical treatment of tumors. However, many patients with triple-negative breast cancer (TNBC) cannot benefit from immunotherapy due to the immune desert type of TNBC, which is unresponsive to immunotherapy. DMKG, a cell-permeable derivative of α-KG, has shown potential to address this issue. METHOD: We investigated the effects of combining DMKG with radioimmunotherapy on TNBC. We assessed the ability of DMKG to promote tumor cell apoptosis and immunogenic death induced by radiotherapy (RT), as well as its impact on autophagy reduction, antigen and inflammatory factor release, DC cell activation, and infiltration of immune cells in the tumor area. RESULT: Our findings indicated that DMKG significantly promoted tumor cell apoptosis and immunogenic death induced by RT. DMKG also significantly reduced autophagy in tumor cells, resulting in increased release of antigens and inflammatory factors, thereby activating DC cells. Furthermore, DMKG promoted infiltration of CD8 + T cells in the tumor area and reduced the composition of T-regulatory cells after RT, reshaping the tumor immune microenvironment. Both DMKG and RT increased the expression of PD-L1 at immune checkpoints. When combined with anti-PD-L1 drugs (α-PD-L1), they significantly inhibited tumor growth without causing obvious side effects during treatment. CONCLUSION: Our study underscores the potential of pairing DMKG with radioimmunotherapy as an effective strategy for treating TNBC by promoting apoptosis, immunogenic death, and remodeling the tumor immune microenvironment. This combination therapy could offer a promising therapeutic avenue for TNBC patients unresponsive to conventional immunotherapy.

"Trojan Horse" Salmonella Enabling Tumor Homing of Silver Nanoparticles via Neutrophil Infiltration for Synergistic Tumor Therapy and Enhanced Biosafety.

Salmonella selectively colonizes into the hypoxic tumor region and exerts antitumor effects via multiple mechanisms, while the tumor colonized Salmonella recruits host neutrophils into the tumor, presenting a key immunological restraint to compromise the Salmonella efficacy. Here, we develop a combinatorial strategy by employing silver nanoparticles (AgNPs) to improve the efficacy and biosafety of Salmonella. The AgNPs were decorated with sialic acid (SA) to allow selective recognition of L-selectin on neutrophil surfaces, based on which the tumor-homing of AgNPs was achieved by neutrophil infiltration in the Salmonella colonized tumor. The tumor-targeting AgNPs exert the functions of (1) local depletion of neutrophils in tumors to boost the efficacy of Salmonella, (2) direct killing tumor cells via L-selectin-mediated intracellular delivery, and (3) clearing the residual Salmonella after complete tumor eradication to minimize the side effects. With a single tail vein injection of such combination treatment, the tumor was eliminated with high biosafety, resulting in a superior therapeutic outcome.

[Research progress of super enhancer in cancer].

Super enhancers (SEs) are composed of clusters of enhancers in close genomic proximity. They constitute a large family of regulatory elements that specify gene expression patterns and cell identity. SE regions consist of unusually strong enrichment of binding sites for transcriptional factors, cofactors, and enhancers associated with epigenetic modifications. SEs play important roles in regulating the aberrant gene expression in tumor cells. Via SEs, cancer cells activate the expression of various oncogenes, and promote cell proliferation, invasion and migration properties. Hence suppression of SEs activities could inhibit the growth and survival of cancer cells. In this review, we summarize the fundamental principles, functions and regulation of super enhancers and therapeutic potential in targeting SEs in cancer cells, thereby introducing and providing new conceptions for development of antineoplastic drugs.

[The sensitivity of transmitted/founder HIV-1 to anti-HIV drugs].

The majority of mucosal HIV-1 infection is initially established by a few HIV-1 viral variants, followed by the development of overt systemic infection, and these viral variants are known as transmitted/ founder viruses(T/F viruses). Investigation of the sensitivity of T/F virus to different anti-HIV-1 drugs will provide the best strategies of pre-exposure prophylaxis(Pr EP) for high-risk groups of HIV-infected patients. Herein we constructed for the first time, a luciferase reporter system for HIV-1 T/F viruses, and then compared the drug sensitivity between T/F viruses and chronic infection virus. The result showed that the 50% inhibitory concentration (IC(50)) of nucleoside reverse transcriptase inhibitors(NRTIs), integrase inhibitors(INIs) and protease inhibitors(PIs) were not significantly different between the T/F viruses and chronic infection viruses of the same subtype(P < 0.05), while non-nucleoside reverse transcriptase inhibitors(NNRTIs) showed a moderate resistance to T/F viruses, with a significant increase in IC50(P < 0.05). The conclusion suggests that when patients are in high-risk or in the acute infection of HIV-1, NNRTIs should be avoided in the first-line antiretroviral therapy regimens.

Rhynchophylline Protects Against the Amyloid ß-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats.

Accumulated soluble amyloid ß (Aß)-induced aberrant neuronal network activity has been recognized as a key causative factor leading to cognitive deficits which are the most outstanding characteristic of Alzheimer's disease (AD). As an important structure associated with learning and memory, the hippocampus is one of the brain regions that are impaired very early in AD, and the hippocampal CA1 region is selectively vulnerable to soluble Aß oligomers. Our recent study showed that soluble Aß1-42 oligomers induced hyperactivity and perturbed the firing patterns in hippocampal neurons. Rhynchophylline (RIN) is an important active tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla which is a traditional Chinese medicine and often used to treat central nervous system illnesses such as hypertension, convulsions, tremor, stroke etc. Previous evidence showed that RIN possessed neuroprotective effects of improving the cognitive function of mice with Alzheimer-like symptoms. In the present study, we aimed to investigate the protective effect of RIN against soluble Aß1-42 oligomers-induced hippocampal hyperactivity. The results showed that (1) the mean frequency of spontaneous discharge was increased by the local application of 3 µM soluble Aß1-42 oligomers; (2) 30 µM RIN did not exert any obvious effects on basal physiological discharges; and (3) treatment with RIN effectively inhibited the soluble Aß1-42 oligomers-induced enhancement of spontaneous discharge, in a concentration-dependent manner with an IC50 = 9.0 µM. These in vivo electrophysiological results indicate that RIN can remold the spontaneous discharges disturbed by Aß and counteract the deleterious effect of Aß1-42 on neural circuit. The experimental findings provide further evidence to affirm the potential of RIN as a worthy candidate for further development into a therapeutic agent for AD.

[Identification and characterization of HIV-1 transmitted /founder viruses].

During the spread of human immunodeficiency virus type 1 (HIV-1) in the mucosa, the entire genetic diversity of the viruses is significantly reduced. The vast majority of HIV-1 mucosal infections are established by one or a few viruses and ultimately develop into systemic infections, thus the initial virus is called transmitted/founder virus (T/F virus). The study of T/F virus will benefit understanding its key characteristics resulting in successful viral replication in the new host body, which may provide novel strategies for the development of AIDS vaccines, pre-exposure prophylaxis and other therapeutic interventions. In this review, we summarize the discovery and evolutionary characteristics of T/F virus as well as early immune response after HIV-1 infection, which will establish the basis to explore the features of T/F viruses.

Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G2arrest and cell apoptosis.

In the event of acute infection, only a few HIV-1 viral variants can establish the initial productive clinical infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). As one of the accessory proteins of HIV-1, viral protein R (Vpr) plays an important role in viral replication. Therefore, the characterization of T/F virus Vpr is beneficial to understand how virus replicates in a new host. In this study, flow cytometry was used to analyze the effect of G2arrest and cell apoptosis induced by the T/F virus Vpr and the chronic strain MJ4 Vpr. The results showed that the ability of T/F virus ZM246 Vpr and ZM247 Vpr inducing G2arrest and cell apoptosis are more potent than the MJ4 Vpr. The comparison of protein sequences indicated that the amino acids of 77, 85 and 94 contain high freqency mutations, suggesting that these sites may be involved in inducing G2arrest and cell apoptosis. Taken together, our work suggests that in acute infections, T/F viruses increase the capacity of G2arrest and cell apoptosis and promote viral replication and transmission in a new host by Vpr genetic mutation.

Synaptic mechanisms underlying thalamic activation-induced plasticity in the rat auditory cortex.

Electrical stimulation of ventral division of medial geniculate body (MGBv) neurons evokes a shift of the frequency-tuning curves of auditory cortical (AC) neurons toward the best frequency (BF) of the stimulated MGBv neurons (frequency-specific plasticity). The shift of BF is induced by inhibition of responses at the BF of the recorded AC neuron, with coincident facilitation of responses at the BF of the stimulated MGBv neuron. However, the synaptic mechanisms are not yet understood. We hypothesize that activation of thalamocortical synaptic transmission and receptor function may contribute to MGBv stimulation-induced frequency-specific auditory plasticity and the shift of BF. To test this hypothesis, we measured changes in the excitatory postsynaptic currents in pyramidal neurons of layer III/IV in the auditory cortex following high-frequency stimulation (HFS) of the MGBv, using whole cell recordings in an auditory thalamocortical slice. Our data showed that in response to the HFS of the MGBv the excitatory postsynaptic currents of AC neurons showed long-term bidirectional synaptic plasticity and long-term potentiation and depression. Pharmacological studies indicated that the long-term synaptic plasticity was induced through the activation of different sets of N-methyl-d-aspartate-type glutamatergic receptors, γ-aminobutyric acid-type receptors, and type 5 metabotropic glutamate receptors. Our data further demonstrated that blocking of different receptors with specific antagonists significantly inhibited MGBv stimulation-induced long-term plasticity as well as the shift of BF. These data indicate that these receptors have an important role in mediating frequency-specific auditory cortical plasticity.

SARS-CoV-2: pathogenesis, therapeutics, variants, and vaccines.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in December 2019 with staggering economic fallout and human suffering. The unique structure of SARS-CoV-2 and its underlying pathogenic mechanism were responsible for the global pandemic. In addition to the direct damage caused by the virus, SARS-CoV-2 triggers an abnormal immune response leading to a cytokine storm, culminating in acute respiratory distress syndrome and other fatal diseases that pose a significant challenge to clinicians. Therefore, potential treatments should focus not only on eliminating the virus but also on alleviating or controlling acute immune/inflammatory responses. Current management strategies for COVID-19 include preventative measures and supportive care, while the role of the host immune/inflammatory response in disease progression has largely been overlooked. Understanding the interaction between SARS-CoV-2 and its receptors, as well as the underlying pathogenesis, has proven to be helpful for disease prevention, early recognition of disease progression, vaccine development, and interventions aimed at reducing immunopathology have been shown to reduce adverse clinical outcomes and improve prognosis. Moreover, several key mutations in the SARS-CoV-2 genome sequence result in an enhanced binding affinity to the host cell receptor, or produce immune escape, leading to either increased virus transmissibility or virulence of variants that carry these mutations. This review characterizes the structural features of SARS-CoV-2, its variants, and their interaction with the immune system, emphasizing the role of dysfunctional immune responses and cytokine storm in disease progression. Additionally, potential therapeutic options are reviewed, providing critical insights into disease management, exploring effective approaches to deal with the public health crises caused by SARS-CoV-2.

PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer.

BACKGROUND: Liver cancer is a prevalent and deadly form of cancer with high incidence and mortality rates. The PCMT1 protein has been linked to cell anti-apoptosis and tumor metastasis, but its significance in liver hepatocellular carcinoma (LIHC) remains largely unexplored. METHODS: We conducted a pan-cancer analysis to examine the expression differences of PCMT1. Kaplan-Meier curves were employed to assess the prognostic impact of PCMT1 on LIHC patients, and we investigated the association between PCMT1 and clinical features, which we validated using a GEO therapeutic dataset. Gene enrichment analysis helped identify signaling pathways associated with PCMT1 expression. Moreover, we evaluated the relationship between PCMT1 and immune cell infiltration, as well as the differences in gene mutations between high-expression and low-expression groups. In vitro and in vivo experiments were performed to assess the effect of PCMT1 on tumor cell lines and mouse tumor models, and potential pathways were explored through gene sequencing. RESULT: PCMT1 is highly expressed in most tumors and exhibits a significant association with prognosis in LIHC patients. Pathway enrichment analysis revealed that PCMT1 is involved in cell cycle regulation, immunity, and other processes. Further immune analysis demonstrated that high expression of PCMT1 could reduce tumor-killing immune cell infiltration. In vitro experiments indicated that PCMT1 knockdown could inhibit cancer cell proliferation and migration while promoting apoptosis. In vivo experiments showed that PCMT1 knockdown significantly reduced tumor growth rate, enhanced CD8+T cell infiltration, and increased caspase-3 expression in the tumor area. Gene sequencing suggested that PCMT1 may function through the PI3K-AKT pathway. CONCLUSION: Our findings suggest that PCMT1 acts as a promoter of liver cancer progression and may serve as a novel prognostic indicator and therapeutic target for patients with LIHC.

Persistent left superior vena cava in right hemiarch replacement under deep hypothermic circulatory arrest: A case report.

BACKGROUND: Persistent left superior vena cava (PLSVC), a relatively rare thoracic vascular malformation, can inconvenience perfusionists and operators when encountered during deep hypothermic circulatory arrest (DHCA). CASE SUMMARY: Herein, we describe the case of a patient with concurrent giant aortic arch aneurysm, aortic stenosis, and PLSVC. To treat these conditions, we performed right hemiarch and aortic valve replacements under DHCA. Notably, we applied "bilateral superior vena cava retrograde cerebral perfusion (RCP)" for cerebral protection, which significantly optimized the surgical procedure and reduced the risk of postoperative complications. The patient was discharged 14 d after surgery with no complications. CONCLUSION: Surgical intervention for PLSVC under DHCA can be performed using the bilateral superior vena cava RCP approach.

UPLC-MS/MS method for Icariin and metabolites in whole blood of C57 mice: development, validation, and pharmacokinetics study.

Icariin, a Chinese medicinal herb with significant effects on Alzheimer's disease, lacks pharmacokinetic data in mice. To address this, a UPLC-MS/MS method was developed and validated for quantifying Icariin and its metabolites, Icariside I and Icariside II, in the whole blood of mice. The method processed micro-whole blood from serial collections of the same C57 mouse, with well-fitted linearity (0.25-800 ng mL-1) and intra- and inter-day precision and accuracy within 15%. Short-time and autosampler stability were verified, with acceptable extraction recoveries and matrix effects over 74.55%. After intravenous administration (15 mg kg-1) of Icariin in C57 mice, Icariside I and Icariside II were detected within 2 min. However, after the intragastric administration (30, 90, and 150 mg kg-1) of Icariin in C57 mice, Icariin and Icariside I were not detected, and Icariin was rapidly converted into Icariside II. Furthermore, the Cmax and AUC0-t of three doses (30, 90, and 150 mg kg-1) of Icariside II increased as the dose increased. In conclusion, this method improves the traditional method of collecting only one blood sample from each mouse, detecting Icariin and its metabolites in the whole blood of mice, especially for serial collection of micro-whole blood.

Controversial role of ILC3s in intestinal diseases: A novelty perspective on immunotherapy.

ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment.

Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy.

Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

OBJECTIVE: JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). METHODS: We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. RESULTS: Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. CONCLUSION: MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

Extracellular Polysaccharide from Rhizopus nigricans Inhibits Hepatocellular Carcinoma via miR-494-3p/TRIM36 Axis and Cyclin E Ubiquitination.

Background and Aims: This study was designed to uncover the mechanism for extracellular polysaccharide (EPS1-1)-mediated effects on hepatocellular carcinoma (HCC) development. Methods: HCC cells were treated with EPS1-1, miR-494-3p mimic, sh-TRIM36, and pcDNA3.1-TRIM36. The levels of miR-494-3p and TRIM36 were measured in normal hepatocytes, THLE-2, and HepG2 and HuH7HCC cell lines, along with the protein expression of cyclin D/E and p21. The proliferation, cell cycle, and apoptosis of HCC cells were assayed. The interactions between miR-494-3p and TRIM36, and between TRIM36 and cyclin E were assessed. Finally, the expression and localization of TRIM36 and cyclin E were monitored, and tumor apoptosis was detected, in tumor xenograft model. Results: EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression. miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells. Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the presence of EPS1-1. Overexpression of TRIM36 further consolidated EPS1-1-mediated inhibition of HCC proliferation, cyclin D/E, and the promotion of apoptosis and p21 expression. Those effects were reversed by miR-494-3p overexpression. TRIM36 was a target gene of miR-494-3p, and TRIM36 induced cyclin E ubiquitination. EPS1-1 suppressed cyclin E expression, promoted TRIM36 expression and tumor apoptosis, all of which were abrogated by increasing the expression of miR-494-3p in vivo. Conclusions: EPS1-1 protected against HCC by limiting its proliferation and survival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination.

Vascular bursts-mediated tumor accumulation and deep penetration of spherical nucleic acids for synergistic radio-immunotherapy.

While nanomedicines have attracted great interests for tumor therapy, their targeting and intra-tumoral penetrating efficiencies have been questioned. Here, we report a two-step low-dose radiotherapy (RT) strategy to realize significant accumulation and deep penetration of spherical nucleic acids (SNAs)-based nanomedicine for synergistic radio-immunotherapy. The first step RT was employed to recruit large amounts of macrophages into tumor. The tumor infiltrated macrophages not only served as nanoparticles drug depots, but also elicited dynamic bursts extravasation to enhance nanoparticles accumulation. We optimized the spatiotemporal combination of RT and SNAs administration for higher level of SNAs delivery, and the delivered SNAs promote M2-to-M1 phenotype switch of macrophages to increase phagocytosis of nanoparticles by 6-fold, resulting in positive feedback with even higher accumulation and intra-tumor penetration of SNAs. Through vascular bursts and macrophage repolarization, as high as 25-fold enhancement of nanoparticles accumulation was achieved as compared to passive targeting of nanoparticles, and the nanoparticles were eventually distributed throughout the tumor tissue with efficient deep penetration. Finally, SNAs in tumor simultaneously sensitized the second dose of RT and remodeled tumor immune microenvironment, resulting in a synergistic anticancer therapy in combination of anti-PD-L1 antibody (αPD-L1) with no noticeable side effects caused by either RT or αPD-L1.

Predicting potential distribution of Ziziphus spinosa (Bunge) H.H. Hu ex F.H. Chen in China under climate change scenarios.

Ziziphus spinosa (Bunge) H.H. Hu ex F.H. Chen is a woody plant species of the family Rhamnaceae (order Rhamnales) that possesses high nutritional and medicinal value. Predicting the effects of climate change on the distribution of Z. spinosa is of great significance for the investigation, protection, and exploitation of this germplasm resource. For this study, optimized maximum entropy models were employed to predict the distribution patterns and changes of its present (1970-2000) and future (2050s, 2070s, and 2090s) potential suitable regions in China under multiple climate scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0 & SSP5-8.5). The results revealed that the total area of the present potential suitable region for Z. spinosa is 162.60 × 104 km2, which accounts for 16.94% of China's territory. Within this area, the regions having low, medium, and high suitability were 80.14 × 104 km2, 81.50 × 104 km2, and 0.96 × 104 km2, respectively, with the high suitability regions being distributed primarily in Shanxi, Hebei, and Beijing Provinces. Except for SSP-1-2.6-2070s, SSP-5-8.5-2070s, and SSP-5-8.5-2090s, the suitable areas for Z. spinosa in the future increased to different degrees. Meanwhile, considering the distribution of Z. spinosa during different periods and under different climate scenarios, our study predicted that the low impact areas of Z. spinosa were mainly restricted to Shanxi, Shaanxi, Ningxia, Gansu, Liaoning, Inner Mongolia, and Jilin Provinces. The results of core distributional shifts showed that, except for SSP1-2.6, the center of the potential suitable region of Z. spinosa exhibited a trend of gradually shifting to the northwest.

Preoperative Body Composition Combined with Tumor Metabolism Analysis by PET/CT Is Associated with Disease-Free Survival in Patients with NSCLC.

Objective: To evaluate the relationship between preoperative primary tumor metabolism and body composition in patients with NSCLC and analyze their effects on DFS. Method: A retrospective study was conducted on 154 patients with NSCLC. All patients were scanned by baseline 18F-FDG PET/CT. SUVmax (maximum standard uptake value) of primary tumor, liver SUVmean (mean standard uptake value), and spleen SUVmean were measured by AW workstation. The skeletal muscle area (SMA), skeletal muscle mass index (SMI), skeletal muscle radiation density (SMD), visceral fat area (VFA), visceral adipose tissue index (VATI), and skeletal muscle visceral fat ratio (SVR) were measured by ImageJ software. Kaplan-Meier survival analysis was used to evaluate the impact of the above parameters on DFS. Results: Compared with the low SUVmax group of primary tumors, the mean values of SMA, VFA, and VATI in the high SUVmax group were significantly higher. In addition, there were obvious differences in histopathological type, pathological differentiation, AJCC stage, and T stage between the two groups. Univariate analysis of DFS showed that VFA, VATI, pathological differentiation, tumor SUVmax, AJCC stage, tumor T stage, and N stage all affected the DFS of patients except for the parameters reflecting skeletal muscle content. Multivariate regression analysis showed that only VFA and SUVmax were associated with DFS. Kaplan-Meier survival analysis showed that high SUVmax, low VFA, high T stage, and high N stage were related to the decrease of DFS. Conclusion: ：Preoperative 18F-FDG PET/CT could comprehensively evaluate the primary tumor SUVmax, skeletal muscle, and visceral fat in patients with NSCLC. The combination of primary tumor SUVmax and visceral fat area can well evaluate the prognosis of patients with NSCLC.