A Thiol-Michael Approach Towards Versatile Functionalized Cyclic Titanium-Oxo Clusters.

In expanding our research activities of superlattice engineering, designing new giant molecules is the necessary first step. One attempt is to use inorganic transition metal clusters as building blocks. Efficient functionalization of chemically precise transition metal clusters, however, remains a great challenge to material scientists. Herein, we report an efficient thiol-Michael addition approach for the modifications of cyclic titanium-oxo cluster (CTOC). Several advantages, including high efficiency, mild reaction condition, capability of complete addition, high atom economy, as well as high functional group tolerance were demonstrated. This approach can afford high yields of fully functionalized CTOCs, which provides a powerful platform for achieving versatile functionalization of precise transition metal clusters and further applications.

A Polymer Network Layer Containing Dually Anchored Ionic Liquids for Stable Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries with high sulfur utilization, long-cycle life, and dendrite-free features hold great promise for the development of next-generation energy storage devices of high energy density. Considerable efforts have been committed to solving the polysulfide shuttle problem toward highly stable Li-S batteries. Here, a unique polymer network containing dually anchored ionic liquids (DA-PIL) is devolped to improve the cycling performance and coulombic efficiency of Li-S batteries. This DA-PIL electrolyte incorporates the amphiphilicity of both the polysulfides anion and lithium cation, creating an ionic function layer on polypropylene separator. Noteworthily, the DA-PIL network is "clean" in the sense that no free ionic specifies are introduced to the electrolyte system. The DA-PIL layer not only enables strong supression against polysulfide shuttling but simultaneously allows fast lithium transportation owing to cooperate electrostatic interaction among anchored cations and anions. The DA-PIL layer functionalized on a polypropylene separator can boost excellent stability of Li-S battery with >1600 h cycling test at 0.25 mA cm-2 . The Li-S cell with DA-PIL layer delivers a higher discharge capacity of 827.4 mAh g-1 at 1C. A discharge capacity of 630.6 mAh g-1 is retained after 1000 cycles.

Rash with different types of BCR-ABL inhibitors in chronic myelogenous leukemia: a systematic review and meta-analysis.

Objective: A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using different types of BCR-ABL inhibitors. Methods: Literature published between 2000 and April 2022 were searched using PubMed, Cochrane Library, Embase and ClinicalTrials.gov. Results: A total of 12 studies were included for meta-analysis. The results showed that the incidence of all-grade or high-grade rash associated with new-generation BCR-ABL inhibitors had no significant difference compared with a standard dose of imatinib. Subgroup analysis suggested that, compared with imatinib, the incidence of all grades of rash was higher in the nilotinib, bosutinib and ponatinib groups. Conclusion: For CML patients treated with nilotinib, bosutinib and ponatinib, the occurrence of skin toxicity should not be ignored.

Alpha 2-Heremans-Schmid glycoprotein gene polymorphism (rs4918) is associated with coronary artery calcification in incident peritoneal dialysis patients.

AIM: Coronary artery calcification (CAC) is a common and severe complication in peritoneal dialysis (PD) patients, and it progresses in a majority of patients. Fetuin-A, encoded by the alpha 2-Heremans-Schmid glycoprotein (AHSG) gene, is a serum calcification inhibitor. The study aimed to examine the role of AHSG gene polymorphism rs4918 in CAC and CAC progression of PD patients. METHODS: Incident PD patients at Huashan Hospital Fudan University in China from August 2007 to July 2018 were recruited in this prospective study and followed up for 2 years. Patients underwent CAC measurements at recruitment and 2 years later. AHSG gene polymorphism rs4918 and serum fetuin-A were determined at baseline. The demographic characteristics, clinical data, and laboratory data were collected during the follow-up period. Binary logistic regression was performed to explore the association between rs4918 with CAC and CAC progression. RESULTS: A total of 202 PD patients (112 men, 55.4%) were recruited, with a mean age of 54 ± 16 years. The multivariate logistic regression identified genotype GG as an independent risk factor that correlates to CAC (odds ratio [OR] = 2.153; 95% CI: 1.182-3.925; p = .012) and CAC progression (OR = 2.482; 95% CI: 1.422-4.330; p = .001). The serum fetuin-A level was influenced by the rs4918 variants of AHSG, with a dose-dependent effect depending on the number of the G allele. CONCLUSION: AHSG gene polymorphism rs4918 affects serum fetuin-A levels and is significantly associated with both CAC and CAC progression in a cohort of patients receiving PD.

Plasma fibrinogen: a driver of left ventricular remodeling in patients undergoing peritoneal dialysis and its related risk factors.

BACKGROUND AND AIM: Plasma fibrinogen has been proven to be significantly associated with cardiovascular mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the role of fibrinogen in left ventricular (LV) remodeling and functions in patients on PD, and explore risk factors related to high fibrinogen level. METHODS: From February 2008 to July 2018, adult patients on regular PD for at least 1 month were recruited and followed up for two years. Correlation analysis was performed to explore the fibrinogen level and echocardiography measurements. Pathogenic factors correlated to the left ventricular hypertrophy (LVH) progression were explored by logistic regression models and the role of fibrinogen in it was verified by receiver operating characteristic (ROC) curves. Linear regression models were conducted to identify factors associated with fibrinogen level. RESULTS: A total of 278 patients undergoing PD (168 males, 60.4%) were recruited. Patients were trisected according to fibrinogen levels at baseline. Mean wall thickness (MWT), relative wall thickness (RWT), and left ventricular mass index (LVMI) were positively associated with fibrinogen level while E/A ratio was negatively associated with it. Multivariate logistic regression and ROC curve showed that fibrinogen was an independent risk factor for LVH progression. Multivariate linear regression analysis identified age, total cholesterol (CHO), fasting blood glucose (FBG), and high-sensitivity C-reactive protein (hsCRP) were significantly related to plasma fibrinogen level. CONCLUSIONS: An elevated fibrinogen level was independently associated with LVH progression in patients undergoing PD. Older age, higher level of FBG, CHO, and hsCRP were risk factors for elevated plasma fibrinogen level.

Efficient Photocatalytic Cleavage of Lignin Models by a Soluble Perylene Diimide/Carbon Nitride S-Scheme Heterojunction.

3,4,9,10-Perylenetetracarboxylic dianhydride (PDI) is one of the best n-type organic semiconductors and an ideal light-driven catalyst for lignin depolymerization. However, the charge localization effect and the excessively strong intermolecular aggregation trend in PDI result in rapid electron-hole (e- -h+ ) recombination, which limits photocatalytic performance. Herein, polymeric carbon nitride/polyhedral oligomeric silsesquioxane PDI (p-CN/P-PDI) S-scheme heterojunction photocatalyst was prepared by the solvent evaporation-deposition method for C-C bond selective cleavage of lignin ß-O-4 model. Based on the material characterization results, the synergic role of polyhedral oligomeric silsesquioxane (POSS) and S-scheme heterojunction maintains appropriate aggregation domains, achieves better solar light utilization, faster charge-transfer efficiency, and greater redox capacity. Notably, the 3 % p-CN/P-PDI heterostructure exhibits a remarkable enhancement in cleavage conversion efficiency, achieving approximately 16.42 and 2.57 times higher conversion rates compared to polyhedral oligomeric silsesquioxane modified PDI (POSS-PDI) and polymeric carbon nitride (p-CN), respectively.

Development of emergent ferroelectric nematic liquid crystals with highly fluorinated and rigid mesogens.

The emerging ferroelectric nematic liquid crystals have been attracting broader interests in new liquid crystal physics and their unique material properties. One big challenge for the ferroelectric nematic research is to enrich the material choice, which is now limited to RM734 and DIO families as representatives, in sharp contrast to the enormously diverse variety of the traditional apolar nematic liquid crystals. Here, we report a design of novel ferroelectric nematic materials with highly fluorinated and rigid mesogens. Noteworthily, they show distinct chemical structural features compared with previous aromatic ester-based molecules. The ferroelectric nematic phase was identified and confirmed through rigorous experiments. The bulk polarization was found to become purely along the long axis director, creating giant dielectric anisotropy. This work demonstrates a great potential for expanding ferroelectric nematic material diversity and will accelerate the corresponding application research and technology innovation.

Prognostic values of left ventricular mass index progression in incident peritoneal dialysis patients : a prospective cohort study.

BACKGROUND: Left ventricular hypertrophy (LVH) is common among patients undergoing dialysis. However, the dynamic structural changes of LV are rarely discussed. The study aimed to investigate the prognostic significance of left ventricular mass index (LVMI)-progression in incident peritoneal dialysis (PD) patients, and explore risks factors for LVMI-progression. METHODS: Incident PD patients between February 2008 and July 2018 were recruited. Echocardiography was performed yearly to collect LVMI and evaluate its changes. Participants were divided into three subgroups: group with LVMI-regression, group with LVMI stable and group with LVMI-progression. The end points include all-cause mortality, cardiovascular mortality and cardiovascular events. Cox regression models were performed to identify the associations between LVMI-progression and these endpoints. Multivariate logistic regression was conducted to identify risk factors for LVMI-progression. RESULTS: A total of 216 PD patients (130 men,60.2%) with a mean age of 54.3 ± 16.8 years were recruited. LVMI-progression was identified in 72 patients (33.3%) after PD initiation. The cohort was followed for a median duration of 65.9 months. Multivariable Cox regression analysis revealed that LVMI-progression was an independent predictor of all-cause mortality (HR, 1.419; 95% CI, 1.016-1.982; p = 0.040), cardiovascular mortality (HR, 1.836; 95%CI, 1.084-3.108; p = 0.024), and cardiovascular events (HR, 1.494; 95%CI, 1.063-2.099; p = 0.021). Multivariable logistic regression showed that hemoglobin, ferritin, blood pressure and fibrinogen were significantly associated with LVMI-progression. CONCLUSION: Early LVMI-progression was independently associated with all-cause mortality and cardiovascular outcomes in PD patients. The dynamic monitoring of LVMI might therefore help identify high-risk patients.

Addition of roxadustat to erythropoiesis-stimulating agent (ESA) effectively corrects ESA-hyporesponsive anaemia in patients on peritoneal dialysis.

WHAT IS KNOWN AND OBJECTIVE: Erythropoiesis-stimulating agent (ESA) hyporesponsiveness is an important cause for the undertreatment of anaemia. A decrease in haemoglobin (Hb) levels was observed during the initial stage of the conversion from ESA to roxadustat. The study aims to investigate the effectiveness and safety of adding roxadustat to an ESA for the treatment of ESA-hyporesponsive anaemia in patients on peritoneal dialysis (PD). METHODS: Patients on PD with ESA-hyporesponsive anaemia were enrolled from January 2020 to April 2020 with a 24-week follow-up period. Patients were treated with roxadustat at a starting dose of 50 or 100 mg thrice weekly without changing the ESA dose. Roxadustat and ESA dose adjustments were made as needed to maintain Hb levels within 11.0 to 13.0 g/dl. Efficacy outcomes and safety were assessed. RESULTS AND DISCUSSION: Nine patients were recruited in the study. Both the cumulative responsive rate and maintenance rate of Hb > 11 g/dl were 100%. Six patients required ESA dose reduction from ≥15,000 UI/week to ≤7000 IU/week at week 24. No drug-related severe adverse events were observed in this study. WHAT IS NEW AND CONCLUSION: The addition of roxadustat effectively and smoothly corrected anaemia in patients who were hyporesponsive to ESA, and permitted reduction of the ESA dose.

How Far Can We Push the Rigid Oligomers/Polymers toward Ferroelectric Nematic Liquid Crystals?

The emerging ferroelectric nematic (NF) liquid crystal is a novel 3D-ordered liquid exhibiting macroscopic electric polarization. The combination of the ultrahigh dielectric constant, strong nonlinear optical signal, and high sensitivity to the electric field makes NF materials promising for the development of advanced liquid crystal electroopic devices. Previously, all studies focused on the rod-shaped small molecules with limited length (l) range and dipole moment (µ) values. Here, through the precision synthesis, we extend the aromatic rod-shaped mesogen to oligomer/polymer (repeat unit up to 12 with monodisperse molecular-weight dispersion) and increase the µ value over 30 Debye (D). The NF phase has a widespread existence far beyond our expectation and could be observed in all the oligomer/polymer length range. Notably, the NF phase experiences a nontrivial evolution pathway with the traditional apolar nematic phase completely suppressed, i.e., the NF phase nucleates directly from the isotropic liquid phase. The discovery of thte ferroelectric packing of oligomer/polymer rods not only offers the concept of extending the NF state to oligomers/polymers but also provides some previously overlooked insights in oxybenzoate-based liquid crystal polymer materials.

Ordered Mesoporous Silica Pyrolyzed from Single-Source Self-Assembled Organic-Inorganic Giant Surfactants.

We report the preparation of hexagonal mesoporous silica from single-source giant surfactants constructed via dihydroxyl-functionlized polyhedral oligomeric silsesquioxane (DPOSS) heads and a polystyrene (PS) tail. After thermal annealing, the obtained well-ordered hexagonal hybrid was pyrolyzed to afford well-ordered mesoporous silica. A high porosity (e.g., 581 m2/g) and a uniform and narrow pore size distribution (e.g., 3.3 nm) were achieved. Mesoporous silica in diverse shapes and morphologies were achieved by processing the precursor. When the PS tail length was increased, the pore size expanded accordingly. Moreover, such pyrolyzed, ordered mesoporous silica can help to increase both efficiency and stability of nanocatalysts.

Protective Strategy to Boost the Stability of Aminated Graphene in Fenton-like Reactions.

Improving the stability of aminated metal-free catalysts is a big challenge in Fenton-like reactions. Herein, trinuclear iron cluster (Fe3 cluster)-protected aminated graphene (Fe3-NH2-GR) is designed by a protective strategy. By protecting with the Fe3 cluster, the lone pair electrons of amino groups are protected and the N content of Fe3-NH2-GR can be fixed steadily. In peroxymonosulfate (PMS)-based Fenton-like reactions with a fixed-bed reactor, the lifetime of Fe3-NH2-GR is two times longer than that of aminated graphene (NH2-GR) under the same conditions. The deactivation kinetics shows that both Fe3-NH2-GR and NH2-GR follow zero-order kinetics and the deactivation rate constants of Fe3-NH2-GR are lower than that of NH2-GR at every period. Moreover, Fe3-NH2-GR still maintains 50% phenol degradation after 40 h rather than being constantly deactivated as NH2-GR. This stable activity is attributed to the formation of -O-NO2, while the N content will be lost in NH2-GR. This protective strategy by the Fe3 cluster provides a reliable method to enhance the efficiency and stability of carbon catalysts in Fenton-like reactions.

Effect of -55C/T Polymorphism of Uncoupling Protein 3 Gene on Risk for New-Onset Diabetes in Chinese Peritoneal Dialysis Patients: A Prospective Cohort Study.

BACKGROUND: A high-glucose load in therapy can cause new-onset diabetes (NOD) in peritoneal dialysis (PD) patients. Genetic variability may result in risk modulation. OBJECTIVES: This study aims to investigate the association between -55C/T polymorphism of uncoupling protein 3 (UCP3) gene and the risk of NOD in PD patients. METHODS: Nondiabetic incident PD patients between May 2005 and January 2017 were recruited (n = 154). -55C/T polymorphism of the UCP3 was genotyped in all participants at baseline. The cohort of wild group (-55CC) and mutant group (-55CT or -55TT) was built based on the genotypic difference. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) during the follow-up. Binary logistic regression was performed to explore the association between HOMA-IR and genotypes. Competitive risk analysis was used to analyze the impact of -55C/T polymorphism of UCP3 on risk for NOD. RESULTS: The cohort was followed for up to 164.6 months (median: 58.3 months; interquartile range: 30.7 months). During the follow-up, 14 NODs occurred in the mutant group, while only 3 occurred in the wild group. Patients in the mutant group had higher HOMA-IR (Odd ratio: 2.210; 95% CI: 1.043-4.680; p = 0.038). Genotype with the variant T allele turned out to be an independent predictor for NOD morbidity (HR: 7.639; 95% CI: 1.798-32.451; p = 0.006). CONCLUSIONS: The variant of T allele of UCP3 -55C/T polymorphism was an independent predictor for NOD in PD patients. Early identification of the genotype may provide scientific basis for patients' clinic management.

Association of Ambulatory Blood Pressure with All-Cause Mortality and Cardiovascular Outcomes in Peritoneal Dialysis Patients.

BACKGROUND: Ambulatory blood pressure monitoring is the gold standard for the diagnosis of hypertension, but its effects on all-cause mortality and cardiovascular outcomes in peritoneal dialysis (PD) patients remain uncertain. We aimed to investigate the association between ambulatory blood pressure and clinical outcomes in PD patients. METHODS: A prospective, observational cohort study was conducted in PD patients enrolled from March 2001 to July 2018 and followed until October 2019. Blood pressure was evaluated using 24-h ambulatory blood pressure monitoring. The endpoints included all-cause mortality, cardiovascular mortality, and cardiovascular events. Multivariable Cox regression was used to identify the associations between ambulatory blood pressure and endpoints. Subsequently, multivariable logistic regression was conducted to identify factors associated with elevated pulse pressure (PP). RESULTS: A total of 260 PD patients (154 men, 59.2%) were recruited. The median follow-up duration was 40.7 months. Our studies revealed that PP was an independent predictor of all-cause mortality (hazard ratio [HR], 1.018; 95% CI, 1.001-1.034; p = 0.032), cardiovascular mortality (HR, 1.039; 95% CI, 1.017-1.061; p < 0.001), and cardiovascular events (HR, 1.028; 95% CI, 1.011-1.046; p = 0.001). Systolic blood pressure was an independent predictor of cardiovascular mortality (HR, 1.023; 95% CI, 1.007-1.040; p = 0.005) and cardiovascular events (HR, 1.018; 95% CI, 1.006-1.030; p = 0.003). Vascular calcification was significantly associated with elevated PP (OR, 3.069; 95% CI, 1.632-5.772; p = 0.001). CONCLUSION: 24-h ambulatory PP was the most significant predictor of all blood pressure indicators for clinical outcomes in PD patients.

Prognostic significance of carotid plaque presence in peritoneal dialysis patients and its association with the apolipoprotein B/apolipoprotein A1 ratio.

AIM: Atherosclerosis has been reported as a risk factor for cardiovascular disease in the general population. As a phenotype of atherosclerosis, carotid plaque and its influence factors are rarely discussed among dialysis patients. The study aimed to investigate the prognosis-predictive significance of carotid plaques in patients on peritoneal dialysis (PD), and explore risks factors for carotid plaque presence. METHODS: It was an observational, prospective study. Patients that had undergone stable PD for at least 3 months were recruited and divided into two subgroups: group with carotid plaques and group without carotid plaques. Cox regression model was used to identify independent predictors of all-cause mortality, cardiovascular events (CVEs), and cardiovascular mortality. Pathogenic factors correlated to the plaque-occurrence were explored by logistic regression and verified by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 233 PD patients were recruited. The cohort was followed for up to 86 months. The carotid plaque presence turned out to be an independent risk factor both of CVEs [hazard ratio (HR): 2.659; 95% confidence interval (CI): 1.231-5.741; P = .013] and cardiovascular mortality (HR: 3.716; 95% CI: 1.168-11.823; P = .026). The apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio was significantly associated with the presence of carotid plaques. ROC analysis indicated that the area under the curve of the ApoB/ApoA1 ratio was higher than that of the traditional lipid metabolism index for detecting plaque presence. CONCLUSION: Carotid plaque presence can predict CVEs and cardiovascular mortality in PD patients. The ApoB/ApoA1 ratio is significantly correlated to the carotid plaques and the ApoB/ApoA1 ratio had a greater sensitivity than traditional lipid indices for predicting plaque presence.

Microporous Cyclic Titanium-Oxo Clusters with Labile Surface Ligands.

By using ethylene glycol and monocarboxylic acid as surface ligands, a series of cyclic Ti-oxo clusters (CTOC) with permanent microporosity are successfully synthesized. With a cyclic {Ti32 O16 } backbone made of eight connected Ti4 tetrahedral cages that are arranged in a zigzag fashion, the clusters have a "donut" shape with an inner diameter of 8.3 Å, outer diameter of 26.9 Šand height of 10.4 Å. While both inner and outer walls of the "donut" clusters are modified by double-deprotonated ethylene glycolates, their upper and lower surfaces are bound by carboxylates and mono-deprotonated ethylene glycolates. The clusters are readily packed into one-dimensional tubes which are further arranged in two different modes into crystalline microporous solids with surface areas over 660 m2 g-1 , depending on the surface carboxylates. The solid with olefin-bearing carboxylates exhibits a superior CO2 adsorption capacity of 40 cm3 g-1 at 273 K under 1 atm. Moreover, the mono-deprotonated ethylene glycolates on the clusters are demonstrated to be highly exchangeable by other alcohols, providing a nice platform for creating microporous solids or films with a wide variety of surface functionalities.

Retroperitoneal leakage as an important cause of acquired ultrafiltration decline in peritoneal dialysis: clinical characteristics and related risk factors.

BACKGROUND: Peritoneal dialysis (PD) is a widely-used renal replacement therapy while low ultrafiltration volume usually results in technique failure. Retroperitoneal leakage has been reported to be one of the causes of acquired decline in ultrafiltration. The present study investigated retroperitoneal leakage in PD patients and explored related risk factors. METHODS: This study was designed as a prospective, observational study. A total of 420 PD patients regularly followed up at our center were enrolled from May 2011 to July 2021 and followed until December 2021. Retroperitoneal leakage was determined by magnetic resonance peritoneography and was used as the endpoint. Patients with retroperitoneal leakage were given intermittent PD or temporary hemodialysis (HD) as therapy. Cox regression models were used to identify risk factors for retroperitoneal leakage. RESULTS: The cohort was followed up for up to 125.0 months (median: 46.4 months; interquartile range: 16.6 months). During the follow-up, 68 patients developed retroperitoneal leakage, with 31 (45.6%) cases occurring within the first year after PD initiation. A total of 62 (91.2%) patients recovered from retroperitoneal leakage and resumed their original PD regimen. Multivariate Cox regression analysis revealed that age and gender were independent predictors for retroperitoneal leakage. Younger males were more likely to develop retroperitoneal leakage. In females, waistline and body mass index (BMI) were found to be risk factors for retroperitoneal leakage. CONCLUSIONS: Retroperitoneal leakage was common in PD patients with ultrafiltration insufficiency and was usually reversible after appropriate treatment. Age and gender were independent risk factors for retroperitoneal leakage.

Aortic dissection induced by vascular endothelial growth factor inhibitors.

Vascular endothelial growth factor (VEGF) contributes to angiogenesis and vasculogenesis. The occurrence and progression of tumors are accompanied by angiogenesis. Vascular endothelial growth factor inhibitors (VEGFI) have been used in anti-tumor treatment. However, aortic dissection (AD) is one of the VEGFI-associated adverse reactions with cute onset, rapid progression, and high case fatality rate. We collected case reports of VEGFI related to aortic dissection in PubMed and CNKI (China National Knowledge Infrastructure) from inception to 28 April 2022. Seventeen case reports were selected. The medication included sunitinib, sorafenib, pazopanib, axitinib, apatinib, anlotinib, bevacizumab, and ramucirumab. This review discusses the pathology, risk factors, diagnosis, and treatment of AD. Vascular endothelial growth factor inhibitors are related to aortic dissection. Although current literature lacks clear statistical evidence on the population, we offer points to encourage further confirmation of the best methods of care for these patients.

Efficacy and safety of immune checkpoint inhibitors-combined antiangiogenic drugs in the treatment of hepatocellular carcinoma: A systematic review and meta analysis.

Background: Hepatocellular carcinoma is a pathological type of liver cancer and accounts for the majority of primary liver cancers. We conducted a meta-analysis to evaluate the efficacy and safety of immune checkpoint inhibitors in combination with antiangiogenic drugs in the treatment of hepatocellular carcinoma. Methods: We searched scientific literature databases and clinical trials databases through May 2022 for required studies. Progression-free survival was taken as the main outcome, and overall survival, response rate and adverse events as secondary outcomes. These data were extracted, combined and used for meta-analysis to compare the treatment effect and safety of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced/unresectable/metastatic hepatocellular carcinoma. Results: This study included 3 randomized controlled trials and 6 single-arm trials of immune checkpoint inhibitors in combination with antiangiogenic drugs in hepatocellular carcinoma. Meta-analysis showed that compared with single use, combination of the two can significantly improve PFS (HR=5.93, 95% CI=5.41, 6.45) and OS (HR=15.84, 95% CI=15.39, 16.28). The ORR and DOR of patients with combination therapy were HR=19.11, 95% CI=15.99, 22.22 and HR=12.26, 95% CI=10.32, 14.21, respectively. Common adverse reactions to combination therapy included hypertension (26.8%), diarrhea (23.6%), fatigue (23.8%), decreased appetite (22.8%), hypothyroidism (9.9%), and rash (14.5%). Conclusion: In the treatment of advanced/unresectable/metastatic hepatocellular carcinoma, immune checkpoint inhibitors combined with antiangiogenic drugs achieved better survival benefits than alone. In addition, the combination therapy has tolerable safety.

Development of ferroelectric nematic fluids with giant-ε dielectricity and nonlinear optical properties.

Superhigh-ε materials that exhibit exceptionally high dielectric permittivity are recognized as potential candidates for a wide range of next-generation photonic and electronic devices. In general, achieving a high-ε state requires low material symmetry, as most known high-ε materials are symmetry-broken crystals. There are few reports on fluidic high-ε dielectrics. Here, we demonstrate how small molecules with high polarity, enabled by rational molecular design and machine learning analyses, enable the development of superhigh-ε fluid materials (dielectric permittivity, ε > 104) with strong second harmonic generation and macroscopic spontaneous polar ordering. The polar structures are confirmed to be identical for all the synthesized materials. Furthermore, adapting this strategy to high-molecular weight systems allows us to generalize this approach to polar polymeric materials, creating polar soft matters with spontaneous symmetry breaking.