miR-20a: a key regulator of orthodontic tooth movement via BMP2 signaling pathway modulation.

AIM: In this study, we aimed to establish a rat tooth movement model to assess miR-20's ability in enhancing the BMP2 signaling pathway and facilitate alveolar bone remodeling. METHOD: 60 male SD rats had nickel titanium spring devices placed between their left upper first molars and incisors, with the right side serving as the control. Forces were applied at varying durations (18h, 24h, 30h, 36h, 42h, 1d, 3d, 5d, 7d, 14d), and their bilateral maxillary molars and surrounding alveolar bones were retrieved for analysis. Fluorescent quantitative PCR was conducted to assess miR-20a, BMP2, Runx2, Bambi and Smad6 gene expression in alveolar bone, and western blot was performed to determine the protein levels of BMP2, Runx2, Bambi, and Smad6 after mechanical loading. RESULT: We successfully established an orthodontic tooth movement model in SD rats and revealed upregulated miR-20a expression and significantly increased BMP2 and Runx2 gene expression and protein synthesis in alveolar bone during molar tooth movement. Although Bambi and Smad6 gene expression did not significantly increase, their protein synthesis was found to decrease significantly. CONCLUSION: MiR-20a was found to be involved in rat tooth movement model alveolar bone remodeling, wherein it promoted remodeling by reducing Bambi and Smad6 protein synthesis through the BMP2 signaling pathway.

Selaginellin Inhibits Melanogenesis via the MAPK Signaling Pathway.

Hyperpigmented skin diseases such as melasma, freckles, and melanosis usually mar the appearance of patients. Traditional herbal medicines are highly accepted in inhibiting skin pigmentation, with advantages of high efficiency, low cost, and low side effects. Selaginellin (SEL), one of the active compounds of selaginella, has been proved to be exhibit antineoplastic, antioxidant, antisenescence, and antiapoptosis activities. In this study, we found that SEL can inhibit melanogenesis in vitro and in vivo. A mechanism study found that SEL inhibits melanogenesis through inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, then down-regulating the expression of microphthalmia-associated transcription factor (MITF) and downstream genes tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2). UVB-activated paracrine function of fibroblasts and keratinocytes promotes melanogenesis of melanocytes. Interestingly, SEL antagonizes UVB-activated paracrine function of fibroblasts and keratinocytes. These findings indicate that SEL can be a potential whitening compound to inhibit melanogenesis.

Glycolytic activation of monocytes regulates the accumulation and function of neutrophils in human hepatocellular carcinoma.

BACKGROUND & AIMS: Neutrophils are one of the most abundant components in human hepatocellular carcinoma (HCC) and have been shown to play important roles in regulating disease progression. However, neutrophils are very short-lived cells in circulation, and mechanisms regulating their accumulation and functions in HCC are not yet fully understood. METHODS: Monocytes were purified from non-tumor or paired tumor tissues of patients with HCC, and their production of neutrophil-attracting chemokines was evaluated. Mechanisms regulating the expression of CXCL2/8 by tumor monocytes, and the role of tumor monocyte-derived chemokines and cytokines in modulating neutrophil accumulation and functions were studied with both ex vivo analyses and in vitro experiments. RESULTS: Monocyte-derived CXCL2 and CXCL8 were major factors in regulating the recruitment of neutrophils into tumor milieus. These chemokines, in addition to tumor-derived soluble factors, could inhibit apoptosis and sustain survival of neutrophils, thus leading to neutrophil accumulation in tumor tissues. Moreover, monocyte-derived TNF-α acted synergistically with tumor-derived soluble factors to induce the production of the pro-metastasis factor OSM by neutrophils. Further, the glycolytic switch in tumor-infiltrating monocytes mediated their production of CXCL2 and CXCL8 via the PFKFB3-NF-κB signaling pathway. Accordingly, levels of PFKFB3, CXCL2/CXCL8 production in monocytes and infiltration of OSM-producing neutrophils were positively correlated in human HCC tissues. CONCLUSIONS: Our results unveiled a previously unappreciated link between monocytes and neutrophils in human HCC, identifying possible targets that could be therapeutically exploited in the future. LAY SUMMARY: Neutrophils constitute a major but poorly understood component of human hepatocellular carcinoma (HCC). Herein, we unveil a novel mechanism by which metabolic switching in monocytes promotes the accumulation of neutrophils in the tumors of patients with HCC. Both monocyte-produced chemokines and signals from the tumor microenvironment promote the production of the pro-metastatic factor OSM by neutrophils. These data identify potential targets for immune-based anticancer therapies for HCC.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Predictive value of the albumin-bilirubin grade on long-term outcomes of CT-guided percutaneous microwave ablation in intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. RESULTS: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. CONCLUSIONS: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

A Cation-Exchange Approach for the Fabrication of Efficient Methylammonium Tin Iodide Perovskite Solar Cells.

Tin-based halide perovskite materials have been successfully employed in lead-free perovskite solar cells, but the overall power conversion efficiencies (PCEs) have been limited by the high carrier concentration from the facile oxidation of Sn2+ to Sn4+ . Now a chemical route is developed for fabrication of high-quality methylammonium tin iodide perovskite (MASnI3 ) films: hydrazinium tin iodide (HASnI3 ) perovskite film is first solution-deposited using presursors hydrazinium iodide (HAI) and tin iodide (SnI2 ), and then transformed into MASnI3 via a cation displacement approach. With the two-step process, a dense and uniform MASnI3 film is obtained with large grain sizes and high crystallization. Detrimental oxidation is suppressed by the hydrazine released from the film during the transformation. With the MASnI3 as light harvester, mesoporous perovskite solar cells were prepared, and a maximum power conversion efficiency (PCE) of 7.13 % is delivered with good reproducibility.

Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers.

PURPOSE: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume. MATERIALS AND METHODS: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15 minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20 mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation. RESULTS: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p < .001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p < .001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p < .001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p < .001). CONCLUSION: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers.

PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103 °C, at both 30 W and 60 W, for 30 min. Ablation diameters and volumes were measured by two examiners. RESULTS: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse diameter were observed in the porcine livers during 10% HCl-RFA at 60 W, measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively. CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.

Androgenesis, gynogenesis, and parthenogenesis haploids in cucurbit species.

Haploids and doubled haploids are critical components of plant breeding. This review is focused on studies on haploids and double haploids inducted in cucurbits through in vitro pollination with irradiated pollen, unfertilized ovule/ovary culture, and anther/microspore culture during the last 30 years, as well as comprehensive analysis of the main factors of each process and comparison between chromosome doubling and ploidy identification methods, with special focus on the application of double haploids in plant breeding and genetics. This review identifies existing problems affecting the efficiency of androgenesis, gynogenesis, and parthenogenesis in cucurbit species. Donor plant genotypes and surrounding environments, developmental stages of explants, culture media, stress factors, and chromosome doubling and ploidy identification are compared at length and discussed as methodologies and protocols for androgenesis, gynogenesis, and parthenogenesis in haploid and double haploid production technologies.

[Influencing factors for brain injury in preterm infants].

OBJECTIVE: To investigate the incidence of different types of brain injury in preterm infants and their influencing factors. METHODS: The clinical data and head magnetic resonance imaging (MRI) findings of 239 preterm infants were collected, and the influence of antepartum, intrapartum, and postpartum factors on brain injury in preterm infants was analyzed. RESULTS: The incidence rate of brain injury in preterm infants was 25.5%; among these infants, 10.5% had hemorrhagic brain injury, 10.5% had ischemic brain injury, and 4.6% and hemorrhagic and ischemic brain injury. The infants with a lower gestational age had higher incidence rates of hemorrhagic brain injury and overall brain injury (P<0.01). The incidence rates of ischemic brain injury and hemorrhagic and ischemic brain injury were not correlated with gestational age (P>0.05). The incidence rates of hemorrhagic, ischemic, and overall brain injury were not correlated with birth weight (P>0.05). Multiparity (OR=0.292, 95%CI 0.088-0.972) and cesarean section (OR=0.075, 95%CI 0.015-0.368) were protective factors against brain injury in infants with a gestational age of <34 weeks; cesarean section (OR=0.296, 95%CI 0.131-0.672) was the protective factor against brain injury in infants with a gestational age of ≤34 weeks, and severe infection (OR=8.176, 95%CI 1.202-55.617) was the risk factor. CONCLUSIONS: In order to prevent or reduce the occurrence of brain injury in preterm infants. the gestational age of preterm infants should be prolonged as much as possible and the indications for cesarean section should be grasped. Infections should be prevented and if occurring should be treated actively and effectively.

[Association between maternal pre-pregnancy body mass index and adverse outcomes of late preterm infants].

OBJECTIVE: To study the association between maternal pre-pregnancy body mass index (BMI) and adverse outcomes of late preterm infants (LPI). METHODS: A total of 367 LPI who were born from January 2011 to December 2015 and admitted to the neonatal ward were enrolled. The BMI criteria for Chinese population were used to analyze the factors for maternal pre-pregnancy BMI and its association with adverse outcomes of LPI (1 minute Apgar score ≤7, delivery room resuscitation, hospitalization days after birth >7 days, and ventilation duration ≥6 hours). RESULTS: Of all LPIs, there were 64 LPI (17.4%) in the low maternal pre-pregnancy BMI group, 243 LPI (66.2%) in the normal maternal pre-pregnancy BMI group, and 60 LPI (16.4%) in the high maternal pre-pregnancy BMI group. Low pre-pregnancy BMI was the risk factor for 1 minute Apgar score ≤7 (OR=3.243, 95% CI: 1.102-9.546) and need for delivery room resuscitation (OR=3.492, 95%CI: 1.090-11.190), and high pre-pregnancy BMI was the risk factor for hospitalization days after birth >7 days (OR=1.992, 95%CI: 1.024-3.874). CONCLUSIONS: Abnormal maternal pre-pregnancy BMI has adverse effects on the outcomes of LPI. In order to reduce these adverse outcomes BMI should be controlled within the normal range in pregnant women.

[Effect of caffeine citrate on early pulmonary function in preterm infants with apnea].

OBJECTIVE: To investigate the effect of caffeine citrate treatment on early pulmonary function in preterm infants with apnea. METHODS: Forty preterm infants with apnea were randomly divided into aminophylline treatment group (20 infants) and caffeine citrate treatment group (20 infants). When the preterm infants experienced apnea after birth, they were given aminophylline or caffeine citrate in addition to assisted ventilation with continuous positive airway pressure (NCPAP). After drug discontinuation, pulmonary function was measured and compared between the two groups. RESULTS: After treatment, compared with the aminophylline treatment group, the caffeine citrate treatment group had significantly higher tidal volume, minute ventilation volume, ratio of time to peak tidal expiratory flow to total expiratory time, ratio of volume to peak tidal expiratory flow to total expiratory volume, peak expiratory flow, and breathing flow at 75%, 50%, and 25% of tidal volume (P<0.05). The caffeine citrate treatment group had a significantly shorter time of oxygen use and NCPAP support than the aminophylline treatment group (P<0.01). Compared with the aminophylline treatment group, the caffeine citrate treatment group had a significantly lower frequency of apnea attacks (P<0.01). CONCLUSIONS: In the treatment of apnea in preterm infants, caffeine citrate can improve early pulmonary function and reduce the incidence of apnea.

[Predictive value of qualitative assessment of general movements for adverse outcomes at 24 months of age in infants with asphyxia].

OJBECTIVE: To investigate the predictive value of the qualitative assessment of general movements (GMs) for adverse outcomes at 24 months of age in full-term infants with asphyxia. METHODS: A total of 114 full-term asphyxiated infants, who were admitted to the neonatal intensive care unit between 2009 and 2012 and took part in follow-ups after discharge were included in the study. All of them received the qualitative assessment of GMs within 3 months after birth. The development quotient was determined with the Bayley Scales of Infant Development at 24 months of age. RESULTS: The results of the qualitative assessment of GMs within 3 months after birth showed that among 114 infants, 20 (17.5%) had poor repertoire movements and 7 (6.1%) had cramped-synchronized movements during the writhing movements period; 8 infants (7.0%) had the absence of fidgety movements during the fidgety movements period. The results of development quotient at 24 months of age showed that 7 infants (6.1%) had adverse developmental outcomes: 6 cases of cerebral palsy and mental retardation and 1 case of mental retardation. There was a poor consistency between poor repertoire movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=-0.019; P>0.05). There was a high consistency between cramped-synchronized movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=0.848; P<0.05), and the results of predictive values of cramped-synchronized movements were shown as follows: predictive validity 98.2%, sensitivity 85.7%, specificity 99.1%, positive predictive value 85.7%, and negative predictive value 99.1%. There was a high consistency between the absence of fidgety movements during the fidgety movements period and the developmental outcomes at 24 months of age (Kappa=0.786; P<0.05), and its predictive values were expressed as follows: predictive validity 97.4%, sensitivity 85.7%, specificity 98.1%, positive predictive value 75.0%, and negative predictive value 99.1%. CONCLUSIONS: Cramped-synchronized movements and absence of fidgety movements can predict adverse developmental outcomes at 24 months of age in full-term infants with asphyxia.

USP26 suppresses type I interferon signaling by targeting TRAF3 for deubiquitination.

Deubiquitinating enzymes (DUBs) play a pivotal role in regulating the antiviral immune response by targeting members of the RLR signaling pathway. As a pivotal member of the RLR pathway, TRAF3 is essential for activating the MAVS/TBK-1/IRF3 signaling pathway in response to viral infection. Despite its importance, the function of DUBs in the TRAF3-mediated antiviral response is poorly understood. Ubiquitin-specific protease 26 (USP26) regulates the RLR signaling pathway to modulate the antiviral immune response. The results demonstrate that EV71 infection upregulates the expression of USP26. Knockdown of USP26 significantly enhances EV71-induced expression of IFN-ß and downstream interferon-stimulated genes (ISGs). Deficiency of USP26 not only inhibits EV71 replication but also weakens the host's resistance to EV71 infection. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. Conversely, knockdown of USP26 leads to an increase in the K63-linked polyubiquitination of TRAF3. These findings unequivocally establish the essential role of USP26 in RLR signaling and significantly contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

A Prospective, Single-Arm, Phase 2 Study of Modified Transarterial Chemoembolization Using Low-Dose Chemotherapy with Blank Microspheres Plus Low-Dose Lenvatinib and Microwave Ablation in Patients with Large (≥7 cm) Unresectable Hepatocellular Carcinoma: The TALEM Trial.

Introduction: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods: In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4-8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7-25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1-19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion: BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

Enhanced oxygen evolution and power density of Co/Zn@NC@MWCNTs for the application of zinc-air batteries.

Rechargeable zinc-air batteries (ZABs) are viewed as a promising solution for electric vehicles due to their potential to provide a clean, cost-effective, and sustainable energy storage system for the next generation. Nevertheless, sluggish kinetics of the oxygen evolution reaction (OER), the oxygen reduction reaction (ORR) at the air electrode, and low power density are significant challenges that hinder the practical application of ZABs. The key to resolving the development of ZABs is developing an affordable, efficient, and stable catalyst with bifunctional catalytic. In this study, we present a series of bifunctional catalysts composed of Co/Zn nanoparticles uniformly embedded in nitrogen-doped carbon (NC) and multi-walled carbon nanotubes (MWCNTs) denoted as Co/Zn@NC@MWCNTs. The incorporation of MWCNTs using a facile and non-toxic method significantly decreased the overpotential of the OER from 570 to 430 mV at 10 mA cm-2 and the peak power density from 226 to 263 mW cm-2. Besides, the electrochemical surface area measurements and electrochemical impedance spectroscopy indicate that the three-dimensional (3D) network structure of MWCNTs facilitates mass transport for ORR and reduces electron transfer resistance during OER, leading to a small potential gap of 0.86 V between OER and ORR, high electron transfer number (3.92-3.98) of the ORR, and lowest Tafel slope (47.8 mV dec-1) of the OER in aqueous ZABs. In addition, in-situ Raman spectroscopy revealed a notable decrease in the ID/IG ratio for the optimally configured Co/Zn@NC@MWCNTs (75:25), indicating a reduction in defect density and improved structural ordering during the electrochemical process, which directly contributes to enhanced ORR activity. Hence, this study provides an excellent strategy for constructing a bifunctional catalyst material with a 3D MWCNTs conductive network for the development of advanced ZAB systems for sustainable energy applications.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

A high performance non-enzymatic glucose sensor based on nickel hydroxide modified nitrogen-incorporated nanodiamonds.

A highly selective, sensitive, and stable non-enzymatic glucose sensor based on Ni hydroxide modified nitrogen-incorporated nanodiamonds (Ni(OH)2-NND) was developed. The sensor was fabricated by e-beam evaporation of a thin Ni film on NND followed by the growth of Ni(OH)2 using an electrochemical process. It was found that the Ni film thickness greatly affects the morphology and electro-catalytic activity of the as-synthesized electrode for non-enzymatic glucose oxidation. Owing to its nanostructure characteristics, the best sensor fabricated by 150 nm Ni deposition showed two wide response ranges, namely, 0.02-1 mM and 1-9 mM, with sensitivities of 3.20 and 1.41 mA mM(-1) cm(-2), respectively, and a detection limit of 1.2 µM (S/N = 3). The sensor also showed good long-term stability as well as high selectivity in the presence of interferences such as ascorbic acid, acetaminophen, and uric acid. This finding reveals the possibility of exploiting the NND as an electrochemical biosensor platform where high performance addressable sensor arrays could be built.