Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+-dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.

A novel technique to remove migrated esophageal stent under fluoroscopy.

PURPOSE: To evaluate the efficacy and safety of a novel technique for removal of migrated esophageal stent (MES) under fluoroscopy. METHODS: From January 2009 to April 2023, 793 patients with a dysphagia score of 3-4 underwent esophageal stenting at our center, and 25 patients (mean age: 70.06 years old; male/female: 15/10) underwent stent removal using "loop method" under fluoroscopy. The primary outcomes were technical success and complications. The secondary outcomes were procedure time, radiation exposure, biochemical indicators [white blood cell (WBC), hemoglobin (Hb), platelet (PLT), albumin (ALB), alanine transaminase (ALT), total bilirubin (TB), urea nitrogen (UN) and C-reactive protein] of pre- and post-treatment at 2 weeks. RESULTS: Technical success was 100% without major complications. The mean procedure time was (39.44 ± 9.28) minutes, which showed no statistical significance between benign (n = 5) and malignant (n = 20) group [(42.40 ± 8.85) vs (38.71 ± 9.46) mins, p > 0.05]. The mean radiation exposure was (332.88 ± 261.47) mGy, which showed no statistical significance between benign and malignant group [(360.74 ± 231.43) vs (325.92 ± 273.54) mGy, p > 0.05]. Pre- and post-procedure Hb [(114.46 ± 11.96) vs. (117.57 ± 13.12) g/L] and ALB [(42.26 ± 3.39) vs. (44.12 ± 3.77) g/L] showed significant difference (p < 0.05), while WBC, PLT, CRP, and ALT showed no significance (p > 0.05). CONCLUSION: Fluoroscopy-guided "Loop method" for MES removal is an effective and safe alternative technique.

False-negative factors of percutaneous transluminal clamp biopsy for suspected malignant biliary stricture: 194 cases analyzed from a single center.

OBJECTIVE: To study the predictive factors of false negatives in the diagnosis of biliary stricture (BS) by percutaneous transluminal clamp biopsy (PTCB). METHOD: From January 2016 to January 2021, 194 patients with a high suspicion of malignant tumors due to BS underwent PTCB during biliary drainage at our department. The final diagnosis was confirmed by postoperative pathology, other tissue or cell evidence, or medical imaging follow-up. Univariate and multivariate regression analyses were performed on the pathological results, summarizing the independent risk factors for false-negative value (FNV) to help further clinical diagnosis and treatment. RESULTS: Of the 194 cases, 176 and 18 cases were finally diagnosed as malignant and benign BS, respectively, compared to 144 and 50 cases by PTCB, including 32 false-negative cases. The sensitivity, specificity, false-positive value, and FNV of PTCB were 81.8%, 100%, 0%, and 18.2%, respectively. Multivariate analysis showed that non-cholangiocarcinoma BS was an independent risk factor for FNV of PTCB (odds ratio 7.5 (95% CI 1.74-32.6), p < 0.01). CONCLUSION: PTCB is an effective minimally invasive interventional technique for BS diagnosis. Non-cholangiocarcinoma BS is an independent risk factor for FNV. CRITICAL RELEVANCE STATEMENT: Identifying factors that are predictive of false-negative results by percutaneous transluminal clamp biopsy in the setting of biliary stricture may have a guiding effect on clinical practice. KEY POINTS: • Factors predictive of false negatives in the diagnosis of biliary stricture etiology by PTCB may aid in the interpretation of results. • Non-cholangiocarcinoma BS is an independent risk factor for FNV on PTCB. • PTCB is an effective minimally invasive interventional technique for BS diagnosis.

Clinical application of the retrograde track method in reopening dysfunctional biliary stents.

Background: Biliary stent dysfunction is challenging to treat in clinic. The retrograde track method (RTM) has a promising clinical application in the reopening of dysfunctional biliary stents. This study aimed to evaluate the clinical value of the RTM in reopening dysfunctional biliary stents. Methods: From February 2013 to January 2020, 151 patients underwent percutaneous transhepatic biliary interventional procedures for reopening dysfunctional biliary stents at the First Affiliated Hospital of Zhengzhou University, and 25 patients (12 females, 13 males; mean age 63.12 years old) underwent the RTM after anterograde reopening dysfunction biliary stent failure. Technical success, clinical success, irradiation dose, procedure time, complications, and overall survival (OS) were recorded, and levels of total bilirubin (TBIL), direct bilirubin (DB), alanine aminotransferase (ALT), albumin (ALB), and carbohydrate antigen-199 (CA-199) were compared before treatment and 1 month after treatment. Results: The technical and clinical success rates were 100% and 96%, respectively, and the irradiation dose and procedure times were 774.07±330.80 mGy and 45.16±9.48 min, respectively. Two patients (8%) experienced major complications. The median OS was 10.73 months [95% confidence interval (CI): 9.37-12.09]. Compared with pretreatment values, the mean levels at 1 month after RTM administration for TBIL (189.47±59.20 vs. 44.65±16.12 µmol/L), DB (144.21±55.83 vs. 27.95±13.86 µmol/L), ALT (89.62±30.85 vs. 49.44±14.25 U/L), and CA-199 (584.59±269.82 vs. 176.76±100.68 U/mL) showed significant decreases, while that of ALB (36.32±2.05 vs. 40.22±1.95 g/L) showed a significant increase (all P values <0.05). Conclusions: RTM is an effective alternative treatment method when anterograde reopening of a dysfunctional biliary stent occurs.

Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Efficacy and safety of raltitrexed-eluting CalliSpheres® bead transarterial chemoembolization in patients with intermediate-stage hepatocellular carcinoma: a single-arm, prospective study.

Background: The most common loadable chemotherapeutic drugs in drug-eluting bead transarterial chemoembolization (DEB-TACE) include doxorubicin, epirubicin, etc. CalliSpheres® beads have exhibited efficient loadability and eluting characteristics for raltitrexed as well as in vitro and animal experiments. However, the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) remain unclear. Objectives: To assess the efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage HCC. Design: The study was conducted as a single-arm prospective study. Methods: This study was a prospective, single-arm trial conducted between June 2019 and June 2022. CalliSpheres® beads loaded with raltitrexed were used in the DEB-TACE procedure. The follow-up lasted for at least 1 year or until death. The primary endpoint was overall survival (OS), and the secondary endpoints were time to progression (TTP), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results: The 6-month ORR and disease control rates were 90.1% and 93.8%, respectively. The median OS was 33.0 months. The 1-, 2-, and 3-year survival rates were 95.1%, 82.1%, and 43.6%, respectively. Child-Pugh class and bilobar disease occurrence were identified as independent OS predictors. The median TTP and PFS were 22.7 and 19.8 months, respectively. Eleven (11.5%) patients experienced at least one grade 3 AE, and serious AEs were reported in five participants (5.2%). No patient experienced grade 4 or 5 AEs. Conclusion: Raltitrexed-loaded DEB-TACE is feasible, safe, and effective in patients with intermediate-stage HCC. Trial registration: This trial was registered at www.chictr.org.cn under the identifier: 1900024097 on 25 June 2019.

Efficacy and safety of raltitrexed-loaded DEB-TACE in patients with intermediate-stage hepatocellular carcinoma The utility of raltitrexed-loaded CalliSphere® beads in drug-eluting bead transarterial chemoembolization (DEB-TACE) has been demonstrated in in vitro and animal experiments. However, its efficacy and safety in patients with intermediate-stage hepatocellular carcinoma (HCC) remain unclear. Hence, this study aimed to assess the efficacy and safety profiles of DEB-TACE for such patients. We discovered that raltitrexed-loaded DEB-TACE led to a 6-month ORR of 90.1%, a median OS of 33.0 months, a median TTP of 22.7 months, and a median PFS of 19.8 months. The 1-, 2-, and 3-year survival rates were 95.1%, 82.1%, and 43.6%, respectively. Factors such as Child-Pugh class and bilobar disease occurrence were identified as independent predictors of OS. The study also showed acceptable safety profiles, with a low incidence of grade 3 adverse events and no grade 4 or 5 adverse events. The results indicated that raltitrexed-eluting CalliSpheres® beads for TACE can be a viable option for treating patients with intermediate-stage HCC.

Celecoxib and cisplatin dual-loaded microspheres synergistically enhance transarterial chemoembolization effect of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is a first-line treatment for intermediate to advanced-stage liver cancer, with drug-eluting microspheres commonly used as embolic agents. However, currently available drug-eluting microspheres suffer from low drug-loading capacity and limited drug options. In this work, we developed polydopamine-modified polyvinyl alcohol dual-drug-loaded microspheres encapsulating celecoxib and cisplatin (referred to as PCDMS). Physicochemical characterization revealed that the surface of the microspheres displayed increased roughness after polydopamine modification, and celecoxib and cisplatin were successfully loaded onto the microsphere surface. In vitro cell experiments demonstrated that the PCDMS significantly inhibited the proliferation and migration of highly metastatic human liver cancer cells (MHCC-97H) and human liver cancer cells (SMMC-7721). Furthermore, the dual-loaded microspheres exhibited remarkable tumor growth inhibition and reshaped the tumor microenvironment in both subcutaneous H22 liver cancer model in Balb/c mice and intrahepatic VX2 tumor model in New Zealand rabbits, demonstrating a synergistic antitumor effect where 1 + 1>2. This work provides a potential therapeutic approach for the treatment of refractory liver cancer and holds significant translational potential.

Robust Micro-Sized and Defect-Rich Carbon-Carbon Composites as Advanced Anodes for Potassium-Ion Batteries.

Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.

Enhanced optical forces on coupled chiral particles at arbitrary order exceptional points.

Exceptional points (EPs)-non-Hermitian degeneracies at which eigenvalues and eigenvectors coalesce-can give rise to many intriguing phenomena in optical systems. Here, we report a study of the optical forces on chiral particles in a non-Hermitian system at EPs. The EPs are achieved by employing the unidirectional coupling of the chiral particles sitting on a dielectric waveguide under the excitation of a linearly polarized plane wave. Using full-wave numerical simulations, we demonstrate that the structure can give rise to enhanced optical forces at the EPs. Higher order EPs in general can induce stronger optical forces. In addition, the optical forces exhibit an intriguing "skin effect": the force approaches the maximum for the chiral particle at one end of the lattice. The results contribute to the understanding of optical forces in non-Hermitian systems and can find applications in designing novel optical tweezers for on-chip manipulations of chiral particles.

"One-stop" synergistic strategy for hepatocellular carcinoma postoperative recurrence.

Residual tumor recurrence after surgical resection of hepatocellular carcinoma (HCC) remains a considerable challenge that imperils the prognosis of patients. Notably, intraoperative bleeding and postoperative infection are potential risk factors for tumor recurrence. However, the biomaterial strategy for the above problems has rarely been reported. Herein, a series of cryogels (coded as SQ-n) based on sodium alginate (SA) and quaternized chitosan (QC) were synthesized and selected for optimal ratios. The in vitro assays showed that SQ-50 possessed superior hemostasis, excellent antibacterial property, and great cytocompatibility. Subsequently, SQAP was constructed by loading black phosphorus nanosheets (BPNSs) and anlotinib hydrochloride (AL3818) based on SQ-50. Physicochemical experiments confirmed that near-infrared (NIR)-assisted SQAP could control the release of AL3818 in photothermal response, significantly inhibiting the proliferation and survival of HUVECs and H22 cells. Furthermore, in vivo studies indicated that the NIR-assisted SQAP prevented local recurrence of ectopic HCC after surgical resection, achieved through the synergistic effect of mPTT and molecular targeted therapy. Thus, the multifunctional SQAP provides a "one-stop" synergistic strategy for HCC postoperative recurrence, showing great potential for clinical application.

PVP with or without microwave ablation for the treatment of painful spinal metastases from NSCLC: a retrospective case-control study.

OBJECTIVE: To compare the clinical efficacy of percutaneous vertebroplasty (PVP) alone and microwave ablation (MWA) combined with PVP for the treatment of painful spinal metastases from non-small cell lung cancer (NSCLC). METHODS: From October 2014 to October 2021, the data of 58 NSCLC patients with refractory painful spinal metastases (visual analog scale score ≥ 5) were retrospectively collected and analyzed. Patients in Group A (n = 30) and Group B (n = 28) received PVP alone and MWA combined with PVP, respectively. The primary endpoint was pain relief. The secondary endpoints were quality of life (QoL), local tumor progression (LTP), and complications. RESULTS: The technical success rate was 100% in both groups. Patients in both groups showed similar pain relief at 1-12 weeks, but patients in Group B still showed sustained pain relief at 24 weeks compared to those in Group A (p = 0.03). The assessment of QoL showed similar changes. LTP (33.00% vs. 7.14%, p = 0.02) and cement leakage rates (40.00% vs. 7.14%, p = 0.03) were lower in Group B. The multivariate analysis demonstrated spinal metastases with a maximum diameter ≤ 3.0 cm (p = 0.027) and MWA combined with PVP (p = 0.028) were two independent protective factors for LTP. For cement leakage, spinal metastases with vertebral body compression (p = 0.019) was an independent risk factor, while MWA combined with PVP (p = 0.042) was an independent protective factor. CONCLUSION: MWA combined with PVP for painful spinal metastases from NSCLC performed more sustained pain relief (>6 months) and ultimately improved QoL with lower LTP and cement leakage rates, compared to PVP alone.

Generalizing factors of COVID-19 vaccine attitudes in different regions: A summary generation and topic modeling approach.

Objective: The goal of this study is to use summary generation and topic modeling to identify factors contributing to vaccine attitudes for three different vaccine brands, with the aim of generalizing these factors across different regions. Methods: A total of 5562 tweets about three vaccine brands (Sinovac, AstraZeneca, and Pfizer) were collected from 14 December 2020 to 30 December 2021. BERTopic clustering is used to group the tweets into topics, and then contrastive learning (CL) is adopted to generate summaries of each topic. The main content of each topic is generalized into three factors that contribute to vaccine attitudes: vaccine-related factors, health system-related factors, and individual social attributes. Results: BERTopic clustering outperforms Latent Dirichlet Allocation clustering in our analysis. It can also be found that using CL for summary generation helped to better model the topics, particularly at the center-point of the clustering. Our model identifies three main factors contributing to vaccine attitudes that are consistent across different regions. Conclusions: Our study demonstrates the effectiveness of deep learning methods for identifying factors contributing to vaccine attitudes in different regions. By determining these factors, policymakers and medical institutions can develop more effective strategies for addressing concerns related to the vaccination process.

Fungal community remediate quartz tailings soil under plant combined with urban sludge treatments.

Introduction: Tailings can cause extensive damage to soil structure and microbial community. Phytoremediation is an effective strategy for remedied tailings soil due to its environmentally friendly and low-cost advantage. Fungi play a crucial role in nutrient cycling, stress resistance, stabilizing soil structure, and promoting plant growth. However, the fungal community variation in phytoremediation remains largely unexplored. Methods: We analyzed soil fungal community based on high-throughput sequencing during three plant species combined with urban sludge to remediate quartz tailings soil. Results: The results indicated that the fungal diversity was significantly increased with plant diversity, and the highest fungal diversity was in the three plant species combination treatments. Moreover, the fungal diversity was significantly decreased with the addition of urban sludge compared with plant treatments, while the abundance of potential beneficial fungi such as Cutaneotrichosporon, Apiotrichum, and Alternaria were increased. Notably, the fungal community composition in different plant species combination treatments were significant difference at the genus level. The addition of urban sludge increased pH, available phosphorus (AP), and available nitrogen (AN) content that were the main drivers for fungal community composition. Furthermore, the fungal networks of the plant treatments had more nodes and edges, higher connectedness, and lower modularity than plant combined with urban sludge treatments. Conclusion: Our results showed that three plant species combined with urban sludge treatments improved fungal community and soil properties. Our results provide insights for quartz tailings soil remediation using plant-fungi- urban sludge.

Predicting early biliary infection after stenting of malignant biliary obstruction: model development and internal validation.

PURPOSE: To analyze the risk factors and develop a clinical prediction model for early biliary infection (EBI) after percutaneous transhepatic biliary stenting (PTBS) in patients with malignant biliary obstruction (MBO). METHODS: The clinical data of 236 patients with MBO treated with PTBS from June 2012 to June 2021 were retrospectively analyzed. Independent risk factors were analyzed by univariate and multivariate logistic regression, and a nomogram model was constructed based on the results. Discrimination, calibration, and clinical usefulness of this model were further assessed. RESULTS: The technical success rate of PTBS was 100%, and EBI after PTBS was 20.3%. Multivariate logistic regression analysis showed that hilar MBO (P = 0.020), diabetes (P = 0.001), previous surgical or endoscopic intervention (P = 0.007), procedure time > 60 min (P = 0.007), and intraprocedural biliary hemorrhage (P = 0.003) were independent risk factors for EBI after PTBS. A nomogram model was developed to predict the probability of EBI. ROC curves showed good discrimination of the model (area under curve = 0.831). The calibration plot indicated that the predicted probability of EBI by this model was in good agreement with the actual probability of EBI. The DCA curves showed that the net benefit of nomogram-assisted decisions was higher than or equal to the net benefit of treatment for all or none at a wide threshold probability (0-0.8). CONCLUSION: The nomogram model based on the above independent risk factors can predict the probability of EBI and model-assisted treatment decisions contribute to improved clinical outcome. Therefore, MBO patients with probability of EBI > 0.20 based on the model should be recommended for perioperative broad-spectrum antibiotics and close monitoring.

Biliary drainage combined with simultaneous 125I seed strand brachytherapy for the treatment of hilar cholangiocarcinoma.

BACKGROUND: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). METHODS: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). CONCLUSION: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.

Food preference strategy of four sympatric rodents in a temperate forest in northeast China.

Rodents are well known as both seed predators and dispersers of various plant species in forest ecosystems, and they play an important role in the regeneration of vegetation. Thus, the research on seed selection and vegetation regeneration by sympatric rodents is an interesting topic. To understand the characteristics of preferences of rodents for different seeds, a semi-natural enclosure experiment was performed with four rodent species (Apodemuspeninsulae, Apodemusagrarius, Tscherskiatriton, and Clethrionomysrufocanus) and the seeds of seven plant species (Pinuskoraiensis, Corylusmandshurica, Quercusmongolica, Juglansmandshurica, Armeniacasibirica, Prunussalicina, and Cerasustomentosa) to investigate the differentiation in niches and patterns of resource utilization of sympatric rodents. The results showed that all the rodents had consumed many seeds of Pi.koraiensis, Co.mandshurica, and Q.mongolica but differed significantly in how they selected the different seeds. The rate of utilization (Ri) of Pi.koraiensis, Co.mandshurica, and Q.mongolica exhibited the highest values. The Ei values indicated that the rodents tested exhibited differences in their priorities used to select the seeds from different plant species. All four species of rodents exhibited obvious preferences for certain seeds. Korean field mice preferentially consumed the seeds of Q.mongolica, Co.mandshurica, and Pi.koraiensis. Striped field mice favor the seeds of Co.mandshurica, Q.mongolica, P.koraiensis, and Nanking cherry. Greater long-tailed hamsters prefer to consume the seeds of Pi.koraiensis, Co.mandshurica, Q.mongolica, Pr.salicina, and Ce.tomentosa. Clethrionomysrufocanus likes to eat the seeds of Pi.koraiensis, Q.mongolica, Co.mandshurica, and Ce.tomentosa. The results supported our hypothesis that sympatric rodents overlap in food selection. However, each rodent species has a marked preference for food selection, and different rodent species differ in their food preferences. This reflects the role of distinct food niche differentiation in their coexistence.

Novel 1,3,4-Thiadiazole Derivatives: Synthesis, Antiviral Bioassay and Regulation the Photosynthetic Pathway of Tobacco against TMV Infection.

Tobacco mosaic virus (TMV) is a systemic virus that poses a serious threat to crops worldwide. In the present study, a series of novel 1-phenyl-4-(1,3,4-thiadiazole-5-thioether)-1H-pyrazole-5-amine derivatives was designed and synthesized. In vivo antiviral bioassay results indicated that some of these compounds exhibited excellent protective activity against TMV. Among the compounds, E2 (EC50 = 203.5 µg/mL) was superior to the commercial agent ningnanmycin (EC50 = 261.4 µg/mL). Observation of tobacco leaves infected with TMV-GFP revealed that E2 could effectively inhibit the spread of TMV in the host. Further plant tissue morphological observation indicated that E2 could induce the tight arrangement and alignment of the spongy mesophyll and palisade cells while causing stomatal closure to form a defensive barrier to prevent viral infection in the leaves. In addition, the chlorophyll content of tobacco leaves was significantly increased after treatment with E2, and the net photosynthesis (Pn) value was also increased, which demonstrated that the active compound could improve the photosynthetic efficiency of TMV-infected tobacco leaves by maintaining stable chlorophyll content in the leaves, thereby protecting host plants from viral infection. The results of MDA and H2O2 content determination revealed that E2 could effectively reduce the content of peroxides in the infected plants, reducing the damage to the plants caused by oxidation. This work provides an important support for the research and development of antiviral agents in crop protection.

Design, Synthesis, and Study of the Dual Action Mode of Novel N-Thienyl-1,5-disubstituted-4-pyrazole Carboxamides against Nigrospora oryzae.

Due to the single target but extensive application of commercialized succinate dehydrogenase inhibitors (SDHIs), resistance problems have gradually become apparent in recent years. To solve this problem, a series of novel N-thienyl-1,5-disubstituted-1H-4-pyrazole carboxamide derivatives were designed and synthesized in this work based on the active skeleton 5-trifluoromethyl-4-pyrazole carboxamide. The bioassay results indicated that some target compounds exhibited excellent in vitro antifungal activities against the eight phytopathogenic fungi tested. Among them, the EC50 values of T4, T6, and T9 against Nigrospora oryzae were 5.8, 1.9, and 5.5 mg/L, respectively. The in vivo protective and curative activities of 40 mg/L T6 against rice infected with N. oryzae were 81.5% and 43.0%, respectively. Further studies revealed that T6 not only significantly inhibited the growth of N. oryzae mycelia but also effectively hindered spore germination and germ tube elongation. Morphological studies using scanning electron microscopy (SEM), fluorescence microscopy (FM), and transmission electron microscopy (TEM) found that T6 could affect the mycelium membrane integrity by increasing cell membrane permeability and causing peroxidation of cellular lipids, and these results were further verified by measuring the malondialdehyde (MDA) content. The IC50 value of T6 against succinate dehydrogenase (SDH) was 7.2 mg/L, lower than that of the commercialized SDHI penthiopyrad (3.4 mg/L). Further, ATP content detection and the results after docking T6 and penthiopyrad suggested that T6 was a potential SDHI. These studies demonstrated that active compound T6 could both inhibit the activity of SDH and affect the integrity of the cell membrane at the same time via a dual action mode, which is different from the mode of action of penthiopyrad. Thus, this study provides a new idea for a strategy to delay resistance and diversify the structures of SDHIs.

Effects of habitat differences on the scatter-hoarding behaviour of rodents (Mammalia, Rodentia) in temperate forests.

To discover the differences in hoarding strategies of rodents for different seeds in different habitats, we labelled and released three different types of seeds, including Pinuskoraiensis, Corylusmandshurica, and Quercusmongolica, in temperate forests of northeastern China and investigated the fate of seeds in four different habitats that included a broad-leaved forest, mixed-forest edge, mixed forest, and artificial larch forest. Our research showed that the hoarding strategy of rodents was found to vary substantially in different habitats. The survival curves of seeds from different habitats showed the same trend, but the rates of consumption in different habitats varied. More than 50% of the seeds in the four habitats were consumed by the tenth day. It took 20 days to consume more than 70% of the seeds. The rate of consumption of P.koraiensis seeds reached 96.70%; 99.09% of the C.mandshurica seeds were consumed, and 93.07% of the Q.mongolica seeds were consumed. The seeds were consumed most quickly in the artificial larch forest. In general, most of the early seeds were quickly devoured. After day 20, the consumption gradually decreased. Rodents found the seeds in the artificial larch forest in a shorter average time than those in the other types of forests. The average earliest discovery time was 1.4 ± 0.9 d (1-3 d). The average earliest discovery time in all the other three habitats exceeded 7 d. The median removal times (MRT) was distributed around the seeds at 14.24 ± 10.53 d (1-60 d). There were significant differences in the MRT among different habitats. It was shortest in the artificial larch forest at 7.67 ± 6.80 d (1-28 d). In contrast, the MRT in the broad-leaved forest was the longest at 17.52 ± 12.91 d (4-60 d). There were significant differences in the MRT between the artificial larch forest and the other habitats. There was less predation of the three types of seeds at the mixed-forest edge, and the most seeds were dispersed. The rates of predation of the P.koraiensis, C.mandshurica, and Q.mongolica seeds were 28.33%, 15.83%, and 44.0%, and 59.17%, 84.17%, and 48.0% of the seeds were dispersed, respectively. The average dispersal distances of all the seeds were less than 6 m, and the longest distance recorded was 18.66 m. The dispersal distances and burial depths differed significantly among the four types of habitats. The distance of seed dispersal was primarily distributed in 1-6 m.