Quantum-Geometry-Induced Anomalous Hall Effect in Nonunitary Superconductors and Application to Sr_{2}RuO_{4}.

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

Electrochemical Visualization of Single-Molecule Thiol Substitution with Nanopore Measurement.

Reactions involving sulfhydryl groups play a critical role in maintaining the structure and function of proteins. However, traditional mechanistic studies have mainly focused on reaction rates and the efficiency in bulk solutions. Herein, we have designed a cysteine-mutated nanopore as a biological protein nanoreactor for electrochemical visualization of the thiol substitute reaction. Statistical analysis of characteristic current signals shows that the apparent reaction rate at the single-molecule level in this confined nanoreactor reached 1400 times higher than that observed in bulk solution. This substantial acceleration of thiol substitution reactions within the nanopore offers promising opportunities for advancing the design and optimization of micro/nanoreactors. Moreover, our results could shed light on the understanding of sulfhydryl reactions and the thiol-involved signal transduction mechanisms in biological systems.

Glioblastoma behavior study under different frequency electromagnetic field.

The tumor-treating fields (TTFields) technology has revolutionized the management of recurrent and newly diagnosed glioblastoma (GBM) cases. To ameliorate this treatment modality for GBM and other oncological conditions, it is necessary to understand the biophysical principles of TTFields better. In this study, we further analyzed the mechanism of the electromagnetic exposure with varying frequencies and electric field strengths on cells in mitosis, specifically in telophase. In reference to previous studies, an intuitive finite element model of the mitotic cell was built for electromagnetic simulations, predicting a local increase in the cleavage furrow region, which may help explain TTFields' anti-proliferative effects. Cell experiments confirmed that the reduction in proliferation and migration of glioma cell by TTFields was in a frequency- and field-strength-dependent manner. This work provides unique insights into the selection of frequencies in the anti-proliferative effect of TTFields on tumors, which could improve the application of TTFields.

miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFBR2

Objective Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor β receptor 2 (TGFβR). Methods We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial–mesenchymal transition (EMT) were assessed, while its effects on TGFβR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay. Results Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFβR2. Conclusion The miRNA miR-17-5p can negatively regulate the expression of TGFβR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC (AU)

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

[Analysis of O3 Sources in Yulin City in Summer Based on WRF-CMAQ/ISAM Model].

In order to have a clearer understanding of the sources of ozone pollution in Yulin City in summer and put forward scientific governance suggestions, the WRF-CMAQ model was used to simulate the O3 concentration in Yulin City and surrounding areas (including Taiyuan City, Xi'an City, Yinchuan City, Hohhot City, and other provincial capital cities) in July 2019. Using the ISAM module, the sources of O3 and its precursors NOx and VOCs in a heavy pollution process in Yulin City were quantified. The results showed that on heavy pollution days, the O3 in Yulin City mainly came from the long-distance transmission outside the simulation area (55.5%), followed by the photochemical reaction of precursors in the simulation area (20.6%, 10.0%, 5.0%, 2.3%, and 2.1%, respectively, in Yulin City, Shanxi Province, Inner Mongolia Autonomous Region, and Shaanxi Province, 1.2% in Gansu Province, Ningxia Hui Autonomous Region, and Henan Province in total), and initial conditions (0.3%); the remaining sources (23.6%) could not be successfully labeled. Yulin City is in the VOCs control area, and its VOCs were composed of paraffin (76.5%), ketones (9.2%), and other types of VOCs (14.3%). The VOCs came from the emission of pollution sources in the simulation area (45.6%, 22.0%, 11.4%, 6.3%, and 5.1%, respectively, in Yulin City, Shanxi Province, Inner Mongolia Autonomous Region, and Shaanxi Province, 0.8% in Gansu Province, Ningxia Hui Autonomous Region, and Henan Province in total) and the long-distance transmission outside the simulation area (27.9%); the remaining 26.5% were not successfully marked. This research showed that to control the O3 pollution in Yulin, not only should the local VOCs emissions be controlled, but the overall planning of VOCs emissions in the peripheral areas should also be done well.

[Analysis of Causes and Sources of Summer Ozone Pollution in Rizhao Based on CMAQ and HYSPLIT Models].

As a typical coastal city, O3 pollution in Rizhao has become increasingly serious in recent years. In order to explore the causes and sources of O3 pollution, IPR process analysis and ISAM source tracking tools based on the CMAQ model were used, respectively, to quantify the contributions of different physicochemical processes and different source tracking areas to O3 in Rizhao. Additionally, by comparing the differences between O3-exceeding days and non-exceeding days, combined with the HYSPLIT model, the regional transportation path of O3 in Rizhao was explored. The results showed that the concentrations of O3, NOx, and VOCs near the coastal areas of Rizhao and Lianyungang were significantly increased on O3 exceedance days compared with those on non-exceedance days. This was mainly because Rizhao was the convergence zone of western, southwestern, and eastern winds on exceedance days, which facilitated the transport and accumulation of pollutants. Process analysis showed that the transport process (TRAN) contribution to the near-surface O3 near the coastal areas of Rizhao and Lianyungang increased significantly on the exceedance days, whereas the contribution to most areas to the west of Linyi decreased. Photochemical reaction (CHEM) had a positive contribution to the O3 concentration in Rizhao during the daytime at all heights, and TRAN had a positive contribution at 0-60 m above the ground, and mainly had a negative contribution above 60 m. The contributions of CHEM and TRAN at 0-60 m above the ground would increase significantly on exceedance days, which was approximately twice that on the non-exceedance days. Source analysis showed that the local sources in Rizhao were the main contribution sources of NOx and VOCs, with the contribution rates of 47.5% and 58.0%, respectively. O3 mainly came from the contribution outside the simulation area (67.5%). The O3 and precursor contributions of the western cities of Rizhao (Weifang, Linyi, etc.) and the southern cities (Lianyungang, etc.) would increase significantly on the days of exceeding the standard. The transportation path analysis showed that the number of exceedances accounted for the largest proportion (11.8%) in the path from the west of Rizhao, which was the main transportation channel of O3 and precursors in Rizhao. This was verified through process analysis and source tracking results, and such trajectories accounted for 13.0% of the total number of trajectories, and their main routes were in the Shaanxi, Shanxi, Hebei, and Shandong regions.

miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFßR2.

OBJECTIVE: Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor ß receptor 2 (TGFßR). METHODS: We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial-mesenchymal transition (EMT) were assessed, while its effects on TGFßR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay. RESULTS: Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFßR2. CONCLUSION: The miRNA miR-17-5p can negatively regulate the expression of TGFßR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC.

Second-line treatment options for hepatocellular carcinoma: current state and challenges for the future.

INTRODUCTION: Since the approval of sorafenib for systemic treatment of advanced hepatocellular carcinoma (HCC), many tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown efficacy and tolerability as first-line treatments. On the other hand, these first-line therapies are associated with low objective response and drug resistance. Many drugs have been successfully tested for second-line treatment of advanced HCC. While the rapid proliferation of second-line treatments for advanced HCC brings hope to patients, it also complicates clinical decision-making. AREAS COVERED: This review aims to facilitate decisions by summarizing the latest guidelines for second-line treatment of HCC in various countries or regions. We then review existing second-line treatment options and discuss challenges that should be addressed in the future. A literature search was conducted in April 2022 of PubMed/Medline, Cochrane library, and abstracts of international cancer meetings. EXPERT OPINION: There is no standard second-line treatment, especially for the case of sequential treatment after atezolizumab plus bevacizumab (atezo+bev) and further studies focused on sequential treatment are warranted in this setting. The design of clinical trials, different etiologies, and complications or quality of life (QoL) are interesting issues in the second-line setting.

Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Current Status and Controversy.

The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13% to 45%. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase inhibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC involving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

Outcomes of Liver Resection for Metabolic Dysfunction-Associated Fatty Liver Disease or Chronic Hepatitis B-Related HCC.

AIMS: This study aims to determine differences in severity of background liver disease at hepatocellular carcinoma (HCC) diagnosis and long-term survival outcomes among patients undergoing liver resection for HCC in the background of metabolic dysfunction-associated fatty liver disease (MAFLD) compared to chronic hepatitis B (CHB) alone or concurrent CHB (CHB/MAFLD). METHODS: Patient demographics and comorbidities, clinicopathologic data, perioperative and long-term outcomes among patients who underwent liver resection for HCC were reviewed. Overall and recurrence-free survival were calculated with the Kaplan-Meier method, with the values compared using the log-rank test. RESULTS: From January 2014 to December 2018, 1325 patients underwent potential curative liver resection of HCC; 67 (5.0%), 176 (13.3%), and 1082 (81.7%) patients had MAFLD alone, CHB concurrent with MAFLD, and CHB alone, respectively. At HCC diagnosis, fewer MAFLD patients had cirrhosis, alpha fetoprotein concentration ≥ 400 ng/mL, tumor size ≥ 5 cm, mulinodular, microvascular invasion, receiving major hepatectomy, and receiving adjuvant transarterial chemoembolization. After a median follow-up of 47 months after liver resection, MAFLD (or MAFLD plus CHB/MAFLD) patients had significantly higher overall and recurrence-free survival than CHB patients before or after propensity score analysis (all P<0.05). CONCLUSION: Patients with HCC in the setting of MAFLD have less-severe background liver disease at HCC diagnosis and better long-term survival after curative liver resection compared to counterparts with CHB/MAFLD or CHB.

Analysis of Clinicopathological Characteristics and Prognosis of Young Patients with Hepatocellular Carcinoma after Hepatectomy.

Background and Aims: This study was designed to analyze the effects of age and clinicopathological characteristics on prognosis of Chinese patients with hepatocellular carcinoma (HCC). Methods: The clinical data of 2032 HCC patients who were first diagnosed with HCC and underwent curative hepatectomy in our hospital between January 2006 and January 2011 were retrospectively analyzed. Results: Younger HCC patients (age <40 years, n=465) had a significantly higher hepatitis B infection rate, larger tumors, higher alpha-fetoprotein levels, higher preoperative liver function, and more frequent vascular invasions than older patients. Most younger patients were suitable for anatomical hepatectomy, and their tumors were found to be at a highly advanced stage. The recurrence-free survival and overall survival rates of younger HCC patients were significantly worse than those of older patients but this difference disappeared after propensity score matching. Multivariate analysis of pre-matched samples showed that age ≤40 years was one of the independent risk factors associated with poor overall survival. Conclusions: Younger patients showed different clinicopathological characteristics than older patients, such as higher rates of hepatitis B infection and advanced tumors. The recurrence-free survival and overall survival rates of younger HCC patients after hepatectomy may be similar to those of older patients.

Dose-Response Between Serum Prealbumin and All-Cause Mortality After Hepatectomy in Patients With Hepatocellular Carcinoma.

BACKGROUND: The relationship between serum prealbumin and the risk of all-cause mortality after hepatectomy in patients with hepatocellular carcinoma (HCC) needs to be evaluated. METHODS: We conducted a retrospective study. A Cox proportional hazards regression model was used to adjust for potential confounders. Prealbumin level was transformed by Z-scores and categorized into quartiles (Q1: <147 mg/L, Q2: 147-194 mg/L, Q3: 194-239 mg/L, Q4: >239 mg/L). We assessed the dose-response relationship between serum prealbumin and the risk of all-cause mortality using a restricted cubic spline model. RESULTS: Data were included from 2,022 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital in China between January 2006 and January 2016. The adjusted hazard ratios (HRs) for increasing quartiles of serum prealbumin were 0.78 [95% confidence interval (CI): 0.64-0.95] for Q2, 0.66 (0.53-0.81) for Q3, and 0.51 (0.41-0.64) for Q4 in the Cox model (all P < 0.001). Serum prealbumin showed an L-shaped, non-linear dose-response relationship with the risk of all-cause mortality (P < 0.001). Among patients whose serum prealbumin was below 250 mg/L, risk of all-cause mortality decreased by 27% (95% CI: 18-36%) per increase of one standard deviation (69.8 mg/L) in serum prealbumin. CONCLUSIONS: Levels of serum prealbumin under 250 mg/L may be considered dangerous with respect to all-cause mortality after hepatectomy in HCC patients. Serum prealbumin may be useful as a prognostic marker in HCC patients undergoing hepatectomy.

Purification, identification and characterization of an esterase with high enantioselectivity to (S)-ethyl indoline-2-carboxylate.

OBJECTIVE: To purify an esterase which can selectively hydrolyze (R,S)-ethyl indoline-2-carboxylate to produce (S)-indoline-2-carboxylic acid and characterize its enzymatic properties. RESULTS: An intracellular esterase from Bacillus aryabhattai B8W22 was isolated and the purified protein was identified as a carboxylesterase by MALDI-TOF mass spectrometry. The enzyme (named BaCE) was 59.03-fold purification determined to be of approximately 35 kDa. Its specific activity was 0.574 U/mL with 20% yield. The enzyme showed maximum activity at pH 8.5 and 30 °C and was stable at 20-30 °C using pNPB as the substrate. The Km, Vmax, kcat and kcat/Km of the esterase were 0.52 mM, 6.39 µM/min, 26.87 min-1 and 51.67 mM/min, respectively. The esterase demonstrated high enantioselectivity toward (S)-ethyl indoline-2-carboxylate with 96.55% e.e.p at 44.39% conversion, corresponding to an E value of 133.45. CONCLUSIONS: In this study, a new esterase BaCE with an apparent molecular mass of 35 kDa was purified to homogeneity for the first time. The esterase from Bacillus aryabhattai B8W22 was isolated with a purification more than 59-fold and a yield of 20% by anion exchange chromatography and hydrophobic interaction chromatography. And its biochemical characterization were described in detail with pNPB as substrate. It displayed high enantioselectivity toward (S)-ethyl indoline-2-carboxylate. We next plan to highly express esterase BaCE in Escherichia coli, and apply it to industrial production of (S)-indoline-2-carboxylic acid.

Association of serum adiponectin levels with artherosclerosis and the metabolic syndrome in obese children.

BACKGROUND: The atherosclerotic process starts at an early age and is linked to obesity. However, the exact pathophysiological mechanism is poorly understood. OBJECTIVE: To investigate the relationship between serum adiponectin and metabolic syndrome and early arteriosclerosis. SUBJECTS: 176 obese and 88 normal children. METHODS: Ultrasound measurement was performed to investigate IMT, FMD, carotid artery compliance (CAC). Adiponectin was measured by enzyme-linked immunosorbent assay. RESULTS: Adiponectin levels correlated negatively with obese markers, blood pressure, fasting insulin, high sensitive CRP, HOMA-IR and IMT; marginally positively associated with CAC and HDL-c. The risk of metabolic syndrome increased 3.43 times when adiponectin levels were less than 7060 ng/ml. Heavy obesity, hypertension, low HDL-c, fasting hyperinsulin, High LDL-c and metabolic syndrome percentage were different in three groups according to the cut-off value of adiponectin. CONCLUSIONS: Low adiponectin levels are associated with a high incidence of metabolic syndrome.