Search

Zemin Ou, Yun You, Hong Yi, Xiaoqian Liu, Yan Tong, Dewen Liu, Jinyu Wang Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dewen Liu; Jinyu Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, People’s Republic of China, Email dwliu@icmm.ac.cn; wangjinyu@icmm.ac.cnIntroduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.Keywords: nanomedicine, brain delivery, angiopep-2, echinacoside, Parkinson’s disease, liposomes

Shuxiu Xiao,1,* Lili Lu,1,* Zhiyuan Lin,2,* Xinming Ye,3 Sheng Su,3 Chenlu Zhang,4 Yang You,4 Wei Li,4 Xiaowu Huang,3 Weizhong Wu,5 Yuhong Zhou1,4 1Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 5Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhong Zhou; Weizhong Wu, Email zhou.yuhong@zs-hospital.sh.cn; wu.weizhong@zs-hospital.sh.cnBackground: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC.Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI.Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells.Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy. Keywords: hepatocellular carcinoma, layilin, CD8+ T cell exhaustion, prognosis

Zihui Yuan,* Chao Du,* Yun You,* Jian Wang Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Wang, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +11-86-15902735929, Email jianwang1030@126.comPurpose: Iliac limb occlusion (ILO) is a serious complication of endovascular abdominal aneurysm repair (EVAR). This study aimed to identify predictive factors for ILO derived from aortoiliac morphology, endovascular procedure-related parameters, and aneurysmal remodeling characteristics.Patients and Methods: Patient demographics, pre-EVAR anatomical characteristics of the aneurysm, endovascular procedure details, and post-EVAR aneurysmal remodeling outcomes were analyzed and compared using univariate analysis. Statistically significant factors were subsequently subjected to Cox regression and Kaplan–Meier analyses.Results: Between January 2013 and April 2022, 66 patients were included in this study. Fourteen patients presented with ILO and were compared with 52 control patients with patent endograft limb over at least 1-year of follow-up. The tortuosity indices of the common iliac artery (CIA) and endograft iliac limb to vessel oversizing were significantly larger in the ILO group than in the patent endograft limb group. The CIA index of tortuosity ≥ 1.08, and endograft iliac limb to vessel oversizing ≥ 18.8% were independent predictors for ILO. During the follow-up of all patients, the proximal aortic neck and CIA diameters increased, aneurysm sac diameter decreased, and aortic neck and aortic length increased. The aortoiliac length increased over time in patients with patent endograft limb but not in patients with ILO. A change in the lowest renal artery-left iliac bifurcation distance ≦0.07 mm increased the risk of ILO.Conclusion: ILO is predisposed to occur when the CIA index of tortuosity ≥ 1.08 and endograft iliac limb to vessel oversizing ≥ 18.8% are present. Significant aortoiliac remodeling, including proximal aortic neck dilatation, neck straightening, aneurysmal sac regression, iliac artery enlargement, and aortic lengthening, occurs after EVAR. Aortoiliac elongation was observed in patients with patent endograft limb, but not in patients with ILO. ILO was associated with a change in the lowest renal artery–left iliac bifurcation from the postoperative measurements ≦ 0.07 mm.Keywords: abdominal aortic aneurysm, endovascular abdominal aneurysm repair, iliac limb occlusion, aortoiliac anatomy, aneurysmal remodeling, oversizing, aortoiliac tortuosity

Understanding reaction kinetics can provide valuable information for the design and optimization of a reaction process. In this study, the reduction degree and carbonitriding ratio of TiO2 in the CH4-H2-N2 system were investigated to understand the kinetics of carbonitriding reduction. The experimental results revealed the following important findings. The reduction degree of TiO2 increased significantly within the temperature range of 1000°C to 1200°C. At the same time, the duration of complete carbonitride time decreased with increasing temperature. However, it was found that excessively high temperatures (1200°C) had a detrimental effect on the degree of reduction. Consequently, the optimal reduction temperature was set at 1100°C, in order to achieve a balance between reduction degree and reaction time. The process of carbonitride reduction of TiO2 in the CH4-H2-N2 system corresponded to the unreacted nuclear model, where the process was mainly controlled by chemical reactions. A calculated apparent activation energy of 99.35 kJ/mol was obtained for the carbonitriding reduction process. The identification of the optimal reduction temperature and the dominant role of chemical reactions provide valuable insights for the design and optimization of carbonitriding processes with titanium compounds.

Zhimei Zhao,1,* Xiang Han,1,* Yunhong You,1 Jiankang Zhang,2 Keke Nie,1 Youxin Ji1 1Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, Qingdao City, People’s Republic of China; 2Department of Medicine, Qingdao Medical College, Qingdao University, Qingdao City, People’s Republic of China*These authors contributed equally to this workCorrespondence: Keke Nie; Youxin Ji, Department of Oncology, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital, 127 Si Liu South Road, Shibei District, Qingdao City, 266042, People’s Republic of China, Tel + (86)532-6866-5078, Fax + (86)532-8486-3506, Email niekekeqd@163.com; mdji001@gmail.comBackground: We study the characteristics and outcomes in lung cancer patients with COVID-19 Omicron variant infection.Methods: Hospitalized lung cancer patients with advanced-stage disease and laboratory-confirmed COVID-19 Omicron infection were included. Pneumonitis involving at least 25% of lung parenchyma on CT scans, accompanied by symptoms and oxygen saturation below 93%, were criteria for enrollment. Pneumonitis severity was graded using CTCAE v5.0. Treatment included Paxlovid, prednisolone, anticoagulation, and ventilation. Initial data, radiographic findings, and outcomes were compared. Logistic regression was employed to determine risk factors for in-hospital mortality.Results: Fifteen patients (median age: 65 years; 80.0% males) were included. 73.3% improved and were discharged, 20.0% died, and 6.7% remained intubated. Initial symptoms included cough (100.0%), fever (73.3%), and shortness of breath (53.3%). Symptoms resolved in discharged patients. Median fever duration was 3.5 days, and respiratory symptom recovery took 26 days. Three patients died due to respiratory failure from Omicron pneumonia. Lower oxygen saturation, reduced lymphocyte/neutrophil ratio on day 7, and diffuse bilateral lung lesions were poor prognostic factors.Conclusion: This study underscores the importance of prompt intervention and early diagnosis for lung cancer patients infected with the COVID-19 Omicron variant. Lower oxygen saturation, decreased lymphocyte/neutrophil ratio on day 7, and diffuse lung lesions on CT scans were associated with worse outcomes. Clinicians should prioritize timely and comprehensive management to improve survival rates in this population.Keywords: COVID-19 omicronvariant, lung cancer, oxygen saturation, lymphocyte and neutrophils ratio, chest CT scan

Yajing You,1,&ast; Tao Yang,2,&ast; Shuhang Wei,1 Zongxin Liu,1 Chenxi Liu,1 Zijian Shen,3 Yinuo Yang,1 Yuemin Feng,1 Ping Yao,2 Qiang Zhu1,2 1Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 3Department of Radiology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhu, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email zhuqiang@sdu.edu.cn Ping Yao, Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Email pingyaozh@sina.comPurpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality.Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes.Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p< 0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p< 0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits.Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.Keywords: steatosis, diabetes, obesity, HBe Ag

Xiaoyi Chen,1,2 Jingyu Zhao,3 Yanxue You,1,2 Zelin Li,2 Shuchun Chen2 1Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 3Graduate School, North China University of Science and Technology, Tangshan, 063210, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email chenshuchunwork88@163.comPurpose: Type 2 diabetic retinopathy is a long-term chronic inflammatory disease. The aim of this study was to investigate the relationship between fibrinogen to albumin ratio (FAR) and retinopathy in type 2 diabetic patients.Methods: This was a retrospective study that included 500 patients with type 2 diabetes mellitus (T2DM), and were divided into non-diabetic retinopathy group (NDR, n=297) and diabetic retinopathy group (DR, n=203) according to fundus examination findings, and the DR group was further divided into non-proliferative retinopathy group (NPDR, n=182) and proliferative retinopathy group (PDR, n=21). Baseline data of patients were collected, and the fibrinogen to albumin ratio (FAR) and neutrophil to lymphocyte ratio (NLR) were calculated to analyze the correlation between FAR and NLR and type 2 diabetic retinopathy.Results: The FAR and NLR were significantly higher in the DR group compared with the NDR group (both P < 0.001). Spearman correlation analysis showed that FAR was positively correlated with NLR and DR (P < 0.05). As the FAR quartile increased, the prevalence of DR increased (14.8%, 16.7%, 25.1%, and 43.30%, respectively; P < 0.05). Multifactorial logistic regression analysis showed that FAR, diabetic course, systolic blood pressure (SBP) and diabetic peripheral neuropathy (DPN) were risk factors for the development of DR in patients with T2DM. The area under the ROC curve for FAR to predict DR progression was 0.708, with an optimal critical value of 7.04, and the area under the ROC curve for diabetes duration and SBP to predict DR was 0.705 and 0.588, respectively.Conclusion: Our findings show for the first time that FAR is an independent risk factor for assessing DR in patients with type 2 diabetes.Keywords: fibrinogen to albumin ratio, type 2 diabetes mellitus, diabetic retinopathy, inflammation, influencing factors

Shan Jiang,1,2 Zhaolei Cui,3 Jianfeng Zheng,1 Qiaoling Wu,1 Haijuan Yu,1 Yiqing You,3 Chaoqiang Zheng,3 Yang Sun1 1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of China; 2College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 3Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of ChinaCorrespondence: Yang Sun, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Email sunyang@fjzlhospital.comBackground: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body’s adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors.Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated.Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group.Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.Keywords: ICD, cervical cancer, immunity, prognosis, immunotherapy response

Kai Yue,1,2 Chao Yang,1 Yu You,1,2 Xueying Wang,3 Xinxin Zhang1 1School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, People’s Republic of China; 2Shunde Graduate School of University of Science and Technology Beijing, Shunde, Guangdong Province, 528399, People’s Republic of China; 3School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong Province, 250022, People’s Republic of ChinaCorrespondence: Kai Yue, Email yuekai@ustb.edu.cnBackground: A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods: In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results: The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C– 43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion: The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.Keywords: artificial vessel, drug delivery, nanoparticle, temperature variation, particle–wall adhesion

Meihua Mei,1– 4,&ast; Danping Liu,1– 4,&ast; Xiuxin Tang,1– 4,&ast; Ying You,1– 4 Baogang Peng,5 Xiaoshun He,1– 3 Junqi Huang1– 4 1Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Organ Donation & Transplant Immunology, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial International Cooperation Base of Science & Technology (Organ Transplantation), Guangzhou, 510080, People’s Republic of China; 4Department of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 5Hepatobiliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junqi Huang, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhong Shan Er Lu, Guangzhou, 510080, People’s Republic of China, Tel +86 (20) 28823388 ext. 8670, Email huangjq@mail.sysu.edu.cnPurpose: To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC).Patients and Methods: Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6).Results: 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved.Conclusion: We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.Keywords: hepatocellular carcinoma, cirrhosis, proteomics, metabolomics, microbiomics, vitamin B6

Multidisciplinary management of rectal cancer has rapidly evolved over the last several years. This review describes recent data surrounding total neoadjuvant therapy, organ preservation, and management of lateral pelvic lymph nodes. It then presents our treatment algorithm for management of rectal cancer at The University of Texas MD Anderson Cancer Center in the context of this and other existing literature. As part of this discussion, the review describes how we tailor management based upon both patient and tumor‐related factors in an effort to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Aim: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative‐intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long‐term outcomes following robotic extended resection for colorectal cancer. Method: We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short‐ and long‐term outcomes, using the Kaplan–Meier method to analyse overall and recurrence‐free survival. Results: Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three‐year overall survival was 88% and median progression‐free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. Conclusion: Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer. [ABSTRACT FROM AUTHOR]

We report the phase-resolved spectral results of the first Galactic pulsating ultraluminous X-ray source (PULX) Swift J0243.6+6124, modeling its 2017–2018 outburst peak using data collected by the Hard X-ray Modulation Telescope (Insight-HXMT). The broad energy coverage of Insight-HXMT allows us to obtain a more accurate spectral continuum to reduce the coupling of broad iron line profiles with other components. We use three different continuum spectrum models but obtain similar iron line results. For the first time, we detect the pulse characteristics of the broad iron line in a PULX. The variation in the width and intensity of this iron line with σ ∼ 1.2–1.5 keV has a phase offset of about 0.25 from the pulse phase. We suggest that the uneven irradiation of the thick inner disk by the accretion column produces the modulated variation of the broad iron line. In addition, the nonpulsed narrow line is suggested to come from the outer disk region. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the use of guselkumab as a treatment for moderate-to-severe psoriasis. The study analyzed data from two Phase 3 trials and found that guselkumab was effective and safe in treating psoriasis. The presence of anti-drug antibodies to guselkumab did not significantly impact the clinical response, and most patients had low antibody levels. The study also found that guselkumab concentrations were similar between patients with and without antibodies. The document cautions against comparing antibody development across different studies or treatments. [Extracted from the article]

Net primary productivity is an essential measure of plant biology and the net flow of carbon between the atmosphere and the terrestrial environment. This aids in comprehending how much carbon is fixed by terrestrial plants and the factors that affect it, thus requiring a thorough grasp of net primary productivity dynamics and how they interact with the climate in arid and humid regions. This study applied remote sensing techniques to evaluate the spatial distribution and climatic variables of the net primary productivity in the Niger River Basin, using the Carnegie Ames Stanford Approach model and correlation analysis. The study revealed that the net primary productivity fell from 338.18 gC/m2 in 2000 to 334.44 gC/m2 in 2020. The correlation result shows that while precipitation (R2=0.87) and actual evapotranspiration (R2=0.83) revealed a positive correlation, temperature (R2=0.328), solar radiation (R2=0.585), and potential evapotranspiration (R2=0.78) shows a negative correlation with the net primary productivity. The study shows that precipitation has a major influence on changes in the net primary production of the NRB. The results of the study may help to better understand how climate studies affect environmental ecology while recommending policymakers to safeguard the Niger River Basin from activities that can deteriorate the environment. [ABSTRACT FROM AUTHOR]

A remote sensing strategy was investigated to evaluate how temperature and rainfall affect the deforestation of economically important tree species in Wudil, Kano Nigeria. The research was carried out in Wudil. To assess the vulnerability of the study area to desertification and the abundance of economic tree species. Landsat satellite products (Landsat 5, 7, 8. were used as the sources of remote sensing imageries. These products were sourced for intervals of ten years, from 1986 to 1999, 2006 to 2016, and 2020. Standardized temperature anomaly and precipitation index from 1986 to 2020 were analyzed using primary and secondary data obtained for information on temperature and rainfall, a hundred questionnaires were used to analyze how much anthropogenic activity has contributed to desertification in the area by looking at their socioeconomic activities, roads, and infrastructural development. To determine the quantity, distribution, growth, and yield of all the species, a transect of one square kilometer was surveyed using regional techniques in each of the four cardinal directions. Principal component analysis revealed that the activity variables and activity observations for 1999, 2006, 2016, and 2016 were all negative, while the years 1986 and 2020 were positive. Increased trends in temperature and decreasing trends in rainfall are evident using the Mann-Kendall analysis, with P-values of 0.0 and 0.003, respectively, which are smaller than the alpha value of 0.05. The main causes of drought and desertification vulnerability according to the findings include variations in the characteristics of rainfall, human activities, and overgrazing. More tree-planting initiatives should be encouraged, ideally making them an annual event in the study region. [ABSTRACT FROM AUTHOR]

Copyright of Climacteric is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Currently, woody invasive species cause for environmental and economic impacts and effect on country gross domestic product. This is observed in Borana rangeland where several woody invasive species infestation happened. This paper aimed to estimate environmental and economic cost of woody invasive species focusing on its distribution and abundance using participatory survey approaches. This approach estimates an average cost for each species by a ratio of management costs, and the annually expenditures incurred by a variety of households. Twelve (12) dominating woody invasive species were recorded in Borana rangeland that are encroached major part of grazing area and Acacia species are the most dominant one. Annually, from each household an estimated total of $29.9 million or 1.1 billion Ethiopian birr economic cost was recorded due to encroachment of woody invasive species and annual economic cost per person was around $424 or 15,137 Ethiopian birr. Cost estimates are the highest for Acacia species (Acacia drepanolobium, Acacia bussei and Acacia mellifera) accounting for 66% of the total estimated economic cost, followed by Capparis tomentosa, which also adversely impacts on ecological services. Such economic cost assessment of woody invasive species used as a monetary basis for ranking the species based on their impact and take prioritizing management actions. Further, the cost estimate approach used in this study could help as a model for woody invasive species economic impact assessments in other part of the rangeland area. [ABSTRACT FROM AUTHOR]

NH4+ and Zn2+ are the most abundant cations detected in contaminated groundwater near municipal landfill sites. Remediation strategies were developed accordingly, such as permeable reactive barrier (PRB) that was reported as effective for single contaminant removal with porous reactive materials, including zeolite and activated carbon. However, considering the fact that multiple contaminants coexist in the groundwater, the removal effect of these porous materials and the competitive retention mechanisms between contaminants are unclear. Therefore, this study investigated the removal contributions of zeolite and activated carbon on NH4+ and Zn2+ under single and coexisting conditions. The priorities and competition mechanisms were clarified through batch and column transport tests, microscopic analyses, as well as geochemical reactive transport modeling by PHREEQC. The results indicated that zeolite performed well in removing both contaminants through ion exchange, while activated carbon was only effective in adsorbing Zn2+ through surface complexation. Mixed zeolite and activated carbon promoted each other in NH4+ removal, but inhibited the removal of Zn2+. With the increase of Zn2+ concentration, competitive adsorption occurred that influenced the breakthrough behaviors of both cations. Considering field applications as PRB reactive materials, it is suggested that pure zeolite will be appropriate if NH4+ is the main contaminant, and a mixture of adsorbents with zeolite content larger than 40% can be effective if considerable amounts of heavy metals coexist with NH4+. [ABSTRACT FROM AUTHOR]

Objective: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity. Design: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions. Results: On multivariate analysis, age (=45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (P<0.001). We observed a non-statistically significant trend for Hispanics having a higher and earlier cumulative incidence of adenomas compared to non-Hispanics (P=0.073). No MMR carrier was more likely to develop advanced adenomas. No difference in the incidence of CRC by MMR gene (P=0.198). Conclusion: Screening recommendations for CRC in LS patients should be based on specific MMR variants and should also be tailored to consider patient demographics. [ABSTRACT FROM AUTHOR]