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Xue Ke,1 Li He,2 Jia-Feng Zheng,1 Yong-Hong Lin,1 Fang Wang1 1Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Fang Wang, Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email wangfcd2022@163.comPurpose: Ectopic pregnancy (EP) is rare among patients having received tubal ligation; in these cases, a fertilized ovum is implanted in the proximal tube stump. Distal tubal EP cases in patients having undergone ipsilateral tubal ligation and who have relatively intact contralateral adnexa are extremely rare. Here, we report a case of pregnancy in the distal stump of the ipsilateral fallopian tube following fallopian tubal isthmus ligation.Case Presentation: A 28-year-old woman was admitted after having experienced lower abdominal pain for 10 days and amenorrhea for 1 week and receiving a transvaginal color ultrasonography finding of a heterogeneous echo (2.1 × 1.2 × 1.4 cm) near the left ovary. The patient had a medical history of transvaginal left tubal ligation under single-port laparoscopy for a left hydrosalpinx. Postoperatively, the patient had undergone in vitro fertilization for assisted reproduction. After ovum retrieval, whole-embryo cryopreservation had been performed due to the ovarian hyperstimulation syndrome trend. This pregnancy was natural after embryo cryopreservation. After the patient was admitted, laparoscopic exploration revealed an elevated ampulla in the distal stump of the left fallopian tube. Left salpingectomy with removal of the ectopic pregnancy in the distal remnant tube was performed under the guidance of transvaginal single-port laparoscopy. Serum β-human chorionic gonadotropin levels gradually decreased. Thereafter, the patient underwent two cycles of frozen embryo transfer, both of which resulted in chemical pregnancies.Conclusion: This case suggests that gynecologists should pay attention to the possibility of fallopian tube ectopic pregnancy in the distal tubal segment post-tubal ligation.Keywords: distal stump, ectopic pregnancy, tubal ligation, unilateral salpingectomy, in vitro fertilization

Autoimmunity occurs when the immune system mistakenly attacks the body, but the presence of autoantibodies, such as antinuclear antibodies (ANAs), does not always lead to autoimmune diseases. Globally, autoimmunity is on the rise, influenced by socioeconomic factors, environmental exposure, diet, and stress. Climate change and pollution further exacerbate risks. The COVID-19 pandemic has worsened the issue, with unvaccinated individuals showing higher rates of autoimmune conditions postinfection. Preventive strategies, including healthy diets, stress management, and vaccination, are crucial in combating this growing epidemic. Collaboration between individuals, healthcare providers, and policymakers is critical to mitigate the rise in autoimmune disorders and enhance public health., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Septic acute kidney injury (AKI) is a fatal disease in the intensive care unit, with ferroptosis playing a crucial role in its pathogenesis. Long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in septic-induced AKI inflammation and apoptosis. However, its regulatory role in ferroptosis and underlying mechanisms remain unclear. In vivo and in vitro models of septic AKI were established using cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) challenge, respectively. Serum levels of creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), and inflammatory cytokine in kidney tissues were determined by ELISA kits. Histopathological alterations and apoptosis were evaluated by HE staining and TUNEL. Ferroptosis was accessed by measuring MDA, GSH, Fe 2+ , total and lipid ROS levels, and mitochondrial ultrastructure changes. Target molecular levels were determined using RT-qPCR, Western blotting, and immunofluorescence. Interactions among MALAT1, acyl-CoA synthetase family member 2 (ACSF2) and FUS RNA binding protein (FUS) were validated by RIP and RNA-pull down. MALAT1 level was significantly elevated in both in vivo and in vitro septic AKI models, of which knockdown impeded ferroptosis to alleviate septic AKI. Mechanistically, high MALAT1 expression increased ACSF2 mRNA stability via interaction with FUS. Rescue experiments showed that ACSF2 overexpression partially reversed the ferroptosis inhibition mediated by MALAT1 silencing. MALAT1 induces ferroptosis and exacerbates septic AKI by stabilizing ACSF2 mRNA with the assistance of FUS. These findings provide theoretical evidence for MALAT1 as a potential therapeutic target for septic AKI., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Herein, a label-free single-molecule electrical sensor was first proposed for the ultrasensitive and selective detection of iodide ions in human urine. Single-molecule conductance measurements in different halogen ion solutions via scanning tunneling microscopy break junction (STM-BJ) clearly revealed that I - ions strongly affect the stability and displacement distance (Δ z ) distribution of molecular junctions. Theoretical calculations prove that the specific adsorption of I - ions modifies the surface properties and weakens the molecular adsorption. Furthermore, the average conductance peak area versus the logarithm of the I - ion concentration has a very good linear relationship in the range of 5 × 10 -6 to 5 × 10 -10 M, with a correlation coefficient of 0.99. This quantitative analysis remains valid in the presence of interfering ions of SO 4 2- , ClO 4 - , Br - , and Cl - as well as interfering molecules of ascorbic acid, uric acid, dopamine, and cysteine. A cross-comparison of the human urine detection results of this single-molecule electrical sensor with those of the clinical method of As 3+ -Ce 4+ catalytic spectrophotometry revealed an average difference of 0.9%, which decreased the detection time of 2 h with the traditional method to approximately 15 min. This work proves the promising practical potential of the single-molecule electrical technique for relevant clinical analysis.

Background: The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients., Methods: A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors., Results: In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score <8; 74.10%), while daily exercise in recovery period (OR: 0.457, 95%CI: 0.229 ~ 0.913), a low-fat diet (OR: 0.600, 95%CI: 0.401 ~ 0.898) and the recovery time from 2 to 4 months (OR: 0.639, 95%CI: 0.445 ~ 0.918) were the protective factors., Conclusion: This is the first time to use the C19-YRSm scale to evaluate the health status in China. The study revealed prevalence of persistent symptoms within 120 days after Omicron onset., (© 2024. The Author(s).)

The recent discovery of frustrated Lewis pairs (FLPs) during the activation of small molecules has inspired extensive research across the full span of chemical science. Owing to the nature of weak interactions, it is experimentally challenging to directly observe and modulate FLP at the molecular scale. Here we design a boron cluster anion building block (B 10 H 8 2- ) and organic amine cations ([NR 4 ] + , R=-CH 3 , -C 2 H 5 ) as the FLP to prove the feasibility of controlling their interaction in the electric double layer (EDL) via an electrochemical strategy. In situ single-molecule electrical measurements and Raman monitoring of B 10 H 8 2- -[NR 4 ] + FLP formed at the positively charged Au(111) electrode surface, in contrast to the free-standing B 10 H 8 2- near or below the potential of zero charge (PZC). Furthermore, this FLP chemistry leads to a shift in the local density of states of boron clusters towards the E F for enhancing electron transport, providing a new prototype of a reversible single-cluster switch that digitally switches upon controlling FLP chemistry in the electric double layer., (© 2024 Wiley-VCH GmbH.)

Background: Ischaemia-reperfusion injury (IRI) is a critical complication post-limb replantation. The oxidative stress and cellular apoptosis due to IRI considerably hinder the healing process. This study aimed to investigate the modulatory effects of pre-perfusion with hydrogen-rich heparin sodium on the nuclear factor erythroid 2-related factor 2 (NRF2)/haeme oxygenase-1 (HO-1) pathway and its potential mechanisms in mitigating skeletal muscle IRI post-limb replantation., Methods: Forty healthy Sprague-Dawley rats (250-300 g) were classified into five groups (n = 8 each): normal control, IRI + heparin sodium pre-perfusion (heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion (hydrogen-rich heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion + NRF2 inhibitor (hydrogen-rich heparin + all-trans retinoic acid [ATRA] group), and IRI + heparin sodium pre-perfusion + NRF2 inhibitor (heparin + ATRA group). The activation of the NRF2/HO-1 pathway in skeletal muscle IRI was evaluated based on HO-1 expression using western blotting and immunofluorescence. Furthermore, haematoxylin and eosin staining and transmission electron microscopy were employed to determine the histopathological characteristics. Additionally, superoxide dismutase and malondialdehyde levels in skeletal muscle tissue were measured to assess antioxidant capacity and the degree of oxidative stress damage. Tissue hypoxia was assessed based on hypoxia-inducible factor 1-alpha expression, whereas apoptosis markers BCL-2-associated X protein (BAX) and Caspase-3 in skeletal muscle tissues were analysed using western blotting with terminal deoxynucleotidyl transferase dUTP nick end labelling staining to quantify cell apoptosis., Results: Compared with the control group, the heparin group exhibited significant pathological changes, including inflammatory infiltration and cellular hypertrophy, with increased apoptosis and oxidative stress. Notably, NRF2 suppression aggravated these effects. However, hydrogen-rich heparin sodium prominently activated the NRF2/HO-1 pathway, enhancing antioxidant defence and reducing BAX/Caspase-3-mediated apoptosis, thereby mitigating IRI-induced damage. The use of an NRF2 inhibitor to inhibit NRF2 excitation by hydrogen-rich heparin sodium notably weakened NRF2 activation and the antioxidant response, resulting in a substantial increase in cellular apoptosis., Conclusion: Pre-perfusion with hydrogen-rich heparin sodium markedly diminishes the BAX/Caspase-3-mediated apoptotic pathway in skeletal muscle tissues with IRI through the excitation of the NRF2/HO-1 pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma. Methods: The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53]. Results: A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t =-2.932, P =0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t =-4.45, P <0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%. Conclusions: Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels., Competing Interests: H. Qiu and R. L. Gao received institutional research grants from Biotyx Medical (Shenzhen) Co. Ltd., Shenzhen. China. G. Zhang, D. Y. Zhang, H. P. Qi, and Y. D. Lu are employees of Biotyx Medical (Shenzhen) Co. Ltd. Y. F. Zheng is an editor-in-chief for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All other authors have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene ( TP ) aromatic ring substituted by two dihydrobenzo[b]thiophene ( BT ) groups with ethynyl spacers ( m , n -TP-BT, ( m , n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10 -4.83 G 0 ( 2,4-TP-BT ) < 10 -4.78 G 0 ( 3,4-TP-BT ) < 10 -4.06 G 0 ( 2,3-TP-BT ) < 10 -3.75 G 0 ( 2,5-TP-BT ). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = E F leads the smallest conductance value for 2,4-TP-BT . This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

Objective: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis., Methods: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies., Results: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo ., Conclusions: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

Objective: A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions., Methods: Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels., Results: Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group., Conclusion: Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy., (© 2024. Huazhong University of Science and Technology.)

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING&#95;TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nitrobenzene is currently the most widely used explosive substance, and is known for its high toxicity and mutagenicity. It can cause severe environmental and water pollution, posing a risk to public health. Among various explosives analysis methods, surface-enhanced Raman spectroscopy (SERS) has the advantages of fast analysis speed, low detection cost, and easy operation, and has become one of the most promising analytical detection methods. Here, we present a portable and reliable sol-based SERS method for the detection of trace amounts of 2,4,6-trinitrotoluene (TNT) in different water bodies. The Meisenheimer complex formed by nitrobenzene and hydrazine hydrate can assemble on unmodified Au nanoparticles in a sol via Au-N bonds, enabling rapid detection of TNT in seawater, lake water, and tap water using a portable Raman spectrometer. Experimental results show that this SERS method can complete the detection within a few minutes and the detection sensitivity can reach 0.01 mg L -1 , which is far lower than China's national standard of no more than 0.5 mg L -1 . Furthermore, this method was also successfully applied to detect trace 2,4-dinitrotoluene (2,4-DNT) and picric acid (2,4,6-trinitrophenol) in water, demonstrating its strong applicability for on-site detection of nitrobenzene explosives.

UV and visible photonics enable applications ranging from spectroscopic sensing to communication and quantum information processing. Photonics structures in these wavelength regimes, however, tend to experience higher loss than their IR counterpart. Particularly in the near-UV band, on-chip optical microresonators have not yet achieved a quality factor beyond 1 million. Here, we report ultra-low-loss photonic waveguides and resonators patterned from alumina thin films prepared by a highly scalable atomic layer deposition process. We demonstrate ultra high Q factor of 1.5×10 6 at 390 nm, a record value at UV bands, and 1.9×10 6 at 488.5 nm.

A concise asymmetric total synthesis of (-)-quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3-dipolar cycloaddition reaction of N-heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio-, exo- and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a Rh III -catalyzed C-H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline-pyrrolidine tetracyclic core unit of quinocarcin., (© 2023 Wiley-VCH GmbH.)

The nature of molecule-electrode interface is critical for the integration of atomically precise molecules as functional components into circuits. Herein, we demonstrate that the electric field localized metal cations in outer Helmholtz plane can modulate interfacial Au-carboxyl contacts, realizing a reversible single-molecule switch. STM break junction and I-V measurements show the electrochemical gating of aliphatic and aromatic carboxylic acids have a conductance ON/OFF behavior in electrolyte solution containing metal cations (i.e., Na + , K + , Mg 2+ and Ca 2+ ), compared to almost no change in conductance without metal cations. In situ Raman spectra reveal strong molecular carboxyl-metal cation coordination at the negatively charged electrode surface, hindering the formation of molecular junctions for electron tunnelling. This work validates the critical role of localized cations in the electric double layer to regulate electron transport at the single-molecule level., (© 2023. The Author(s).)

Electroreductive dehalogenation as an efficient and green approach has attracted much attention in pollution remediation. Herein, we have employed a shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique to in situ probe the electroreductive dehalogenation process of aryl halides with thiol groups at Ag/aqueous solution interfaces. It is found that 4-bromothiophenol (BTP) and 4-chlorothiophenol (CTP) can turn into mixed products of 4,4'-biphenyldithiol (BPDT) and thiophenol (TP) as the electrode potential decreases. The conversion ratios estimated from the Raman intensity variations of C-Cl and C-Br vibrations are 44% and 58% for CTP and BTP in neutral solution, respectively. Furthermore, the quantitative analysis of benzene ring vibrations reveals a C-C cross coupling between the benzene free radical intermediate and adjacent TP product, which results in increased selectivity for biphenyl products at negative potentials.

Background: Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis. However, the levels of immunoglobulin (Ig) and complement in patients with hypersplenism associated with cirrhotic portal hypertension remain unclear. This study was undertaken to determine the levels of Ig and complement in these patients, the relationship between these levels and Child-Pugh class and their clinical significance., Aim: To investigate the antibody (Ig) and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and their clinical significance., Methods: Clinical data of 119 patients with hypersplenism associated with cirrhotic portal hypertension were statistically analyzed and compared with those of 128 control patients., Results: IgA and IgG levels in patients with hypersplenism were significantly higher than controls ( P < 0.001). There was no significant difference in IgM between the two groups ( P = 0.109). C3 and C4 levels in patients with hypersplenism were significantly lower than controls ( P < 0.001). As liver function decreased, IgA and IgG levels increased ( P < 0.001), and C3 and C4 levels decreased ( P < 0.001)., Conclusion: Patients with hypersplenism associated with cirrhotic portal hypertension have significantly higher antibody (IgA and IgG) levels and significantly lower complement (C3 and C4) levels, which are both related to liver damage. Clinically, the administration of anti-hepatitis virus agents and protection of liver function should be strengthened., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rational design and constructing earth-abundant electrocatalysts for efficient electrocatalytic water splitting is a crucial challenge. Herein, we report a simple and efficient one-step electrochemical synthetic route of the NiFe 2 O 4 @FeOOH composite electrocatalyst for the oxygen evolution reaction. The unique morphology of the NiFe 2 O 4 nanoflowers loaded on FeOOH nanosheets allows more active sites to be exposed and promote charge transfer as well as gas release, and the resulting electrode enables a current density of 10 mA cm -2 at a low overpotential of 255 mV with outstanding stability at a current density of 100 mA cm -2 for 300 h.

Objective: The aim of the study is to explore the contribution and mechanism of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in pancreatic ductal adenocarcinoma (PDAC) progression., Methods: Expressions of circFGFR1, microRNA (miR)-532-3p, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were assessed by quantitative real-time polymerase chain reaction or in situ hybridization. Fluorescence in situ hybridization determined the subcellular localization of circFGFR1. Immunohistochemistry was used to detect PIK3CB expression in PDAC tissues. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Wound healing, transwell, and flow cytometry assays examined the migration, invasion, and apoptosis. Dual-luciferase and RNA pull-down assay verified the interactions between circFGFR1/PIK3CB and miR-532-3p. In vivo xenograft tumor growth and lung metastasis were assessed in nude mice., Results: Functionally, knockdown of circFGFR1 restrained in vitro PDAC cell growth, migration, invasion, and in vivo xenograft tumor growth and lung metastasis. In addition, circFGFR1 could sponge miR-532-3p to upregulate PIK3CB level. Rescue experiments revealed that the tumor-suppressive effects caused by miR-532-3p mimics could be reversed by circFGFR1 or PIK3CB overexpression., Conclusions: Our data revealed that circFGFR1 driven the malignant progression of PDAC by targeting miR-532-3p/PIK3CB axis, suggesting that inhibition of circFGFR1 might be considered as a therapeutic target for PDAC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Single-molecule recognition and detection with the highest resolution measurement has been one of the ultimate goals in science and engineering. Break junction techniques, originally developed to measure single-molecule conductance, recently have also been proven to have the capacity for the label-free exploration of single-molecule physics and chemistry, which paves a new way for single-molecule detection with high temporal resolution. In this review, we outline the primary advances and potential of the STM break junction technique for qualitative identification and quantitative detection at a single-molecule level. The principles of operation of these single-molecule electrical sensing mainly in three regimes, ion, environmental pH and genetic material detection, are summarized. It clearly proves that the single-molecule electrical measurements with break junction techniques show a promising perspective for designing a simple, label-free and nondestructive electrical sensor with ultrahigh sensitivity and excellent selectivity.

In this study, black carbon (BC) aerosols were continuously observed using a seven-channel aethalometer (AE-33) in Ordos from August 12 to October 4, 2019; using this data combined with article matter (PM), pollutant gas, and meteorological element data; a HYSPLIT model; and potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models, we analyzed the temporal evolution and potential source appointment and main influence areas of BC. The results showed that the average of ρ (BC) was 882 ng·m -3 , accounting for 6.08% of PM 2.5 . The ρ (BC) was mainly concentrated at 200-1000 ng·m -3 , accounting for 55.9% of the total samples. In different BC mass concentration ranges, BC liquid was the mainstay, with an average proportion of 86%. The diurnal variations in BC and PM 2.5 showed unimodal distributions, with peaks at 08:00 and 10:00, respectively, and peak concentrations increased by 24.3% and 47.2%, respectively. The diurnal variation in BC solid showed a bimodal distribution, with peaks at 08:00 and 20:00, respectively. The diurnal variation in the BC liquid showed a unimodal distribution with a peak at 08:00. The strong correlation between BC and NO 2 indicated a greater impact of vehicle emissions on BC concentration, whereas the weak correlation between BC and SO 2 indicated a lower impact of industrial emissions on BC concentration. The dominant air masses affecting the Ordos could be divided into four categories. The southern air masses (35.6%) had the highest mass concentration of atmospheric pollutants, followed by the local air masses (26.9%) and the northwest air masses (18.8%), and the northeast air masses (18.7%) had the lowest mass concentration of pollutants. The influence of the Ordos on the downstream areas was mainly divided into the northeast air masses (40.9%), the northwest air masses (30.4%), and the southeast air masses (28.7%). High CWT value areas of BC were mainly located in the southern Yan'an-Tongchuan-Baoji-Hanzhong areas and Lvliang-Linfen-Sanmenxia-Nanyang areas. They were two long and narrow transmission belts with a weight mass concentration exceeding 1400 ng·m -3 . High CWT value areas of BC had the greatest impact on the Wuhai-Bayannaoer-Baotou-Hohhot regions, with a weight concentration exceeding 900 ng·m -3 . The long-range transportation of BC could reach the Yulin-Yan'an-Tongchuan-Baoji areas in the south, the Shuozhou-Datong-Beijing areas in the east, and the Xilin Gol League-Xing'an League-Hulunbuir areas in the northeast.

Background: Despite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism., Methods: In this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed in vitro ., Results: TCF7 mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4 + and CD8 + T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells., Conclusion: Downregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Shi, Yin, Zheng, Fu, Jiang, Shang and Zhang.)

Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, β-unsaturated piperidinone. Among these, the ortho-fluorine-substituted CN-2F surfaced as a promising lead molecule, which was significantly superior to the parent curcumin in protecting HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide. Mechanically, by virtue of its Michael receptor units and ortho-substituted mode, CN-2F activated Nrf2 signaling by covalently modifying Cys-151 and Cys-288 residues at Keap1, promoting phosphorylation of JNK, ERK and p38, as well as inhibiting Nrf2 degradation. This work reveals the structural determinants and the activity mechanisms of CN-2F as an Nrf2-dependent cytoprotector, and gives useful information on how to design curcumin-inspired Nrf2 activators and cytoprotectors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Probing the adlayer structures on an electrode/electrolyte interface is one of the most important tasks in modern electrochemistry for clarifying the electrochemical processes. Herein, we have combined cyclic voltammetry and electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy techniques to explore the potential-dependent adlayer structures on Au(111) in a room-temperature ionic liquid of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIPF 6 ) without or with pyridine (Py). It is clearly found that the BMI + cations strongly adsorb on the negatively charged surface with a flat-lying orientation, leaving a little space for Py adsorption. Upon increasing the potentials of the electrode, the variations of Raman band intensities and frequencies reveal that the interaction between the BMI + cations and the Au surface becomes weak; meanwhile, the Py adsorption becomes strong, and its geometry turns from flat, tilted to vertical. Finally, BMI + cations desorb and leave plenty of surface sites for Py adsorption in bulk solution, and a N-bonded compact Py adlayer is formed on the very positively charged surface. This causes obvious anodic peaks in cyclic voltammograms, and the peak currents increase with the square root of the scanning rate. The present work provides a fair molecular-level understanding of electrochemical interfaces and molecular adsorption of Py in ionic liquids.

Significant variability issues in metal-molecule contacts, such as adsorption geometry, lead to characteristic variability in the electrical responses of individual molecules. Herein, co-assembling 1-ethylimidazole (EIM) on Au(111) has been shown to be a feasible and effective strategy for tuning the binding configurations of pyridine-linked molecular junctions in the most common aqueous environments and atmospheric environments. The single-molecule conductance measurements clearly show a transition from multiple conductance peaks to a single conductance peak with increasing EIM concentration. Raman spectroscopy and DFT calculations suggest that the thermodynamically favorable EIM adsorbate results in the vertical orientation of the bipyridine.

The electroreductive cleavage of carbon-halogen bonds has attracted increasing attention in both electrosynthesis and pollution remediation. Herein, by employing the in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique, we have successfully investigated the electroreductive dehalogenation process of aryl halides with the thiol group on a smooth Au electrode in aqueous solution at different pH values. The obtained potential-dependent Raman spectra directly reveal a mixture of the reduction products 4,4'-biphenyldithiol (BPDT) and thiophenol (TP). The conversion ratios of the C-Cl and C-Br bonds at pH = 7 are 37% and 55%, respectively. Furthermore, quantitative analysis of the intensity variations of ν (C-Cl), ν (C-Br) and aromatic ν (CC) stretching modes suggests electroreductive dehalogenation via both direct electron transfer reduction and electrocatalytic hydrodehalogenation. Molecular evidence for the C-C cross coupling process through TP reaction with benzene free radical intermediates is found at negative potentials, which leads to the increasing selectivity of biphenyl products.

Objective: To investigate the clinical effect of scar tissue suture at the broken end of Achilles tendon after gastrocnemius aponeurosis release in the treatment of chronic Achilles tendon rupture., Methods: The clinical data of 17 patients with old achilles tendon rupture treated from January 2017 to December 2019 were analyzed retrospectively, including 15 males and 2 females, aged 26 to 53 years with an average of (35.2±11.6) years old, and the time from injury to operation was 37 to 92 days with an average of (49.3±13.3) days. Myerson's classification included 6 cases of typeⅡ and 11 cases of typeⅢ. The defect of the broken end of Achilles tendon was 2 to 5 cm with an average of(4.1±1.5) cm after partial scar tissue was removed. All patients were treated with gastrocnemius aponeurosis, appropriate excision of scar tissue at the broken end of Achilles tendon and direct suture. The continuity and healing of Achilles tendon were evaluated by color Doppler ultrasound 3 months after operation. The ankle plantar flexor strength was measured by ankle plantar flexor strength tester before operation and 1 year after operation. American Orthopaedic Foot and Ankle Society ankle hindfoot score (AOFAS) and Achilles tendon rupture score were used before operation and 1 year after operation Achilles tendon total fracture score (ATRS) was used to evaluate the clinical rehabilitation of Achilles tendon rupture., Results: All patients were followed up for 12 to 18 months with an average of(13.6±1.8) months. The surgical incision healed in stageⅠ. Color Doppler ultrasound showed good continuity of Achilles tendon, local Achilles tendon slightly thickened and irregular fiber direction. The ankle plantar flexor force (92.2±3.9) N at 1 year after operation was significantly higher than that before operation (29.5±4.2) N ( P <0.05);One year after operation, the AOFAS(91.20±3.30) was significantly higher than that before operation (42.20±4.40)( P <0.05);the ATRS (90.70±3.00) was significantly higher than that before operation(40.00±2.90)( P <0.05)., Conclusion: The gastrocnemius aponeurosis release combined with scar suture of Achilles tendon end is an effective technique for the treatment of chronic Achilles tendon rupture, avoid injury to hallux flexor longus or flexor digitorum longus, with the plantar flexor muscle strength of the ankle was recovered well, is an effective method to treat chronic Achilles tendon rupture.

Room-temperature ionic liquids (RTILs) emerged as ideal solvents, and bipyridine as one of the most used ligands have been widely employed in surface science, catalysis, and molecular electronics. Herein, in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and STM break junction (STM-BJ) technique has been employed to probe the electrochemical process of bipyridine at Au(111)/IL interfaces. It is interestingly found that these molecules undertake a redox process with a pair of well-defined reversible peaks in cyclic voltammograms (CVs). The spectroscopic evidence shows a radical cation generated with rising new Raman peaks related to parallel CC stretching of a positively charged pyridyl ring. Furthermore, these electrochemically charged bipyridine is also confirmed by electrochemical STM-BJ at the single-molecule level, which displays a binary conductance switch ratio of about 400% at the redox potentials. This present work offers a molecular-level insight into the pyridine-mediated reaction process and electron transport in RTILs.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 μm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products., Competing Interests: R. L. Gao and H. Qiu received institutional research grants from Lifetech Scientific (Shenzhen) Co. Ltd. and BiotyxMedical (Shenzhen) Co. Ltd., Shenzhen, China. H. P. Qi, L. Qin, W. Q. Zhang, G. Zhang and D. Y. Zhang are employees of BiotyxMedical (Shenzhen) Co. Ltd.. X. L. Shi is employee of Lifetech Scientific (Shenzhen) Co. Ltd.. All other authors have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

The fabrication of solid-state single-molecule switches with high on-off conductance ratios has been proposed to advance conventional technology in areas such as molecular electronics. Herein, we employed the scanning tunneling microscope break junction (STM-BJ) technique to modulate conductance in single-molecule junctions using mechanically induced stretching. Compound 1a possesses two dihydrobenzothiophene (DHBT) anchoring groups at the opposite ends linked with rigid alkyne side arms to form a gold-molecule-gold junction, while 1b contains 4-pyridine-anchoring groups. The incorporation of ferrocene into the backbone of each compound allows rotational freedom to the cyclopentadienyl (Cp) rings to give two distinct conductance states (high and low) for each. Various control experiments and suspended junction compression/retraction measurements indicate that these high- and low-conductance plateaus are the results of conformational changes within the junctions (extended and folded states) brought about by mechanically induced stretching. A high-low switching factor of 42 was achieved for 1a , whereas an exceptional conductance ratio in excess of 2 orders of magnitude (205) was observed for 1b . To the best of our knowledge, this is the highest experimental on-off conductance switching ratio for a single-molecule junction exploiting the mechanically induced STM-BJ method. Computational studies indicated that the two disparate conductance states observed for 1a and 1b result from mechanically induced conformational changes due to an interplay between conductance and the dihedral angles associated with the electrode-molecule interfaces. Our study reveals the structure-function relationship that determines conductance in such flexible and dynamic systems and promotes the development of a single-molecule variable resistor with high on-off switching factors.

Photocatalysis is an efficient and green technology in the environmental protection. Due to the high charge separation and transfer, donor-acceptor (D-A) conjugated polymers attract much attention for their photocatalytic degradations towards organic pollutants. Herein, the authors reported three novel D-A conjugated polymers, named as HPBP, HPTP, and HPF, with heptazine moieties as electron acceptors, while biphenyl, terphenyl, or fluorene moieties as electron donors, respectively, which indeed exhibit a highly efficient photocatalytic degradation towards tetracyclines upon the visible-light irradiation. Among them, the photocatalytic performance of HPF is especially noticeable with the degradation rate up to 87% within 30 min, almost 11 times in comparison to those of pristine g-C 3 N 4 , which is mainly attributed to its high crystallinity and conjugation. For their photocatalytic mechanism, the •O 2 - radical anions are regarded as the active species., (© 2021 Wiley-VCH GmbH.)

Increasing evidence has suggested the crucial role cyclin-dependent kinases (CDKs) in the biology of hepatocellular carcinoma (HCC), a lethal malignancy with high morbidity and mortality. Hence, this study explored the modulatory effect of the putative cyclin-dependent kinase 11B (CDK11B)-mediated ubiquitination on HCC stem cells. The expression of CDK11B, SAM pointed domain-containing ETS transcription factor (SPDEF) and DOT1-like histone lysine methyltransferase (DOT1L) was determined by RT-qPCR and western blot analysis in HCC tissues and cells. The interaction among CDK11B, SPDEF, miR-448, and DOT1L was analyzed by Co-IP, ubiquitination-IP and ChIP assays, whereas their effects on the biological characteristics of HCC stem cells were assessed by sphere formation and colony formation assays. An in vivo xenograft tumor model was developed for validating the regulation of CDK11B in oncogenicity of HCC stem cells. We characterized the aberrant upregulation of CDK11B and downregulation SPDEF in HCC tissues and cells. CDK11B degraded SPDEF through ubiquitin-proteasome pathway, whereas SPDEF could bind to the miR-448 promoter and inhibit the expression of DOT1L by activating miR-448, whereby promoting self-renewal of HCC stem cells. Knockdown of CDK11B attenuated the self-renewal capability of HCC stem cells and their oncogenicity in vivo. These findings highlighted that blocking the CDK11B-induced degradation of SPDEF and enhancing miR-448-dependent inhibition of DOT1L may delay the progression of HCC by restraining self-renewal capability of HCC stem cells, representing novel targets for HCC management., (© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)

LncRNA PVT1 has been demonstrated to be upregulated in acute myeloid leukaemia (AML) patients and indicates a poor prognosis. Nevertheless, its role in AML remains obscure. This study investigated the regulatory role and potential mechanisms of PVT1 in the progression of AML. Expression of PVT1, miR-29 family and WAVE1 was detected by quantitative real-time polymerase chain reaction. CCK8 and EdU assays were performed to assess the proliferation of AML cells. Cell cycle and apoptosis were determined by propidium iodide (PI) staining and Annexin V/PI staining on a flow cytometer. Transwell assay was carried out to evaluate the migration and invasion abilities. The interaction between miR-29 family and PVT1/WAVE1 was confirmed by dual luciferase reporter assay and RNA immunoprecipitation assay. The protein levels of WAVE1, Bcl-2, Bax, cleaved Caspase 3, cyclin D1, and p21 were detected by western blotting. Xenograft transplantation was performed to determine the tumourigenicity of AML cell in vivo. PVT1 expression was significantly increased in AML patient samples and cells, which positively correlated with WAVE1 expression. Silencing of PVT1 restrained growth, migration and invasion, while inducing apoptosis of AML cells. Moreover, PVT1 acted as a sponge for miR-29 family to increase WAVE1 expression in AML cells. Overexpression of WAVE1 partly counteracted PVT1 knockdown-induced anti-tumour effects on AML cells in vitro and xenograft tumour in vivo. PVT1 facilitated the progression of AML via regulating miR-29 family/WAVE1 axis, which supported the conclusion that PVT1 may be a promising therapeutic target for AML., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Mitochondrial dysfunction in proximal tubular epithelial cells is a key event in acute kidney injury (AKI), which is a risk factor for the development of chronic kidney disease (CKD). Apelin is a bioactive peptide that protects against AKI by alleviating inflammation, inhibiting apoptosis, and preventing lipid oxidation, but its role in protecting against mitochondrial damage remains unknown. Herein, we examined the protective effects of apelin on mitochondria in cisplatin-stimulated human renal proximal tubular epithelial cells and evaluated its therapeutic efficacy in cisplatin-induced AKI mice. In vitro, apelin inhibited the cisplatin-induced mitochondrial fission factor (MFF) upregulation and the fusion-promoting protein optic atrophy 1 (OPA1) downregulation. Apelin co-treatment reversed the decreased levels of the deacetylase, Sirt3, and the increased levels of protein acetylation in mitochondria of cisplatin-stimulated cells. Overall, apelin improved the mitochondrial morphology and membrane potential in vitro. In the AKI model, apelin administration significantly attenuated mitochondrial damage, as evidenced by longer mitochondrial profiles and increased ATP levels in the renal cortex. Suppression of MFF expression, and maintenance of Sirt3 and OPA1 expression in apelin-treated AKI mice was also observed. Finally, exogenous administration of apelin normalized the serum level of creatinine and urea nitrogen and the urine levels of NGAL and Kim-1. We also confirmed a regulatory pathway that drives mitochondrial homeostasis including PGC-1α, ERRα and Sirt3. In conclusion, we demonstrated that apelin ameliorates renal functions by protecting tubular mitochondria through Sirt3 upregulation, which is a novel protective mechanism of apelin in AKI. These results suggest that apelin has potential renoprotective effects and may be an effective agent for AKI treatment to significantly retard CKD progression., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is the most common cancer and its prognosis is poor due to metastasis and recurrence. EMT is associated with metastasis. A deep understanding of regulatory mechanism of EMT is critical. LncRNA is involved in regulation of various biological processes including EMT. This study aimed to investigate the regulatory signal axis among lncRNA SNHG12, miR-516a-5p and the target gene HEG1 during EMT. Cell cycle and apoptosis were analyzed by flow cytometry. Tumorigenesis was analyzed by clone formation assay. Wound healing assay and transwell assay was performed to detect migration and invasion, respectively. Interaction among SNHG12, miR-516a-5p and HEG1 were analyzed by dual luciferase assay and RIP assay. We also detected expression of RNA and protein by QPCR and western blotting. Finally, tumor growth was analyzed by tumorigenesis assay in vivo. Ki-67 and HEG1 level in tumor tissues was analyzed by IHC. SNHG12 and HEG1 were upregulated, miR-516a-5p was downregulated in HCC cell lines. SNHG12 could interact with and inhibit miR-516a-5p. MiR-516a-5p could interact with HEG1 and inhibit HEG1 expression. Knock down SNHG12 inhibited proliferation, migration, invasion, EMT and promoted apoptosis of HCC cells. Such effects were antagonized by inhibiting miR-516a-5p. SNHG12 overexpression lead to opposite results. Similar results were observed in mice. SNHG12 could promote EMT in HCC through targeting and inhibiting miR-516a-5p, which eventually upregulated HEG1 expression, in both cell and mice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Clarifying interfacial electronic effects on molecular adsorption is significant in many chemical and biochemical processes. Here, we used STM breaking junction and shell-isolated nanoparticle-enhanced Raman spectroscopy to probe electron transport and adsorption geometries of 4,4'-bipyridine (4,4'-BPY) at Au(111). Modifying the surface with 1-butyl-3-methylimidazolium cation-containing ionic liquids (ILs) decreases surface electron density and stabilizes a vertical orientation of pyridine through nitrogen atom σ-bond interactions, resulting in uniform adsorption configurations for forming molecular junctions. Modulation from vertical, tilted, to flat, is achieved on adding water to ILs, leading to a new peak ascribed to CC stretching of adsorbed pyridyl ring and 316 % modulation of single-molecule conductance. The dihedral angle between adsorbed pyridyl ring and surface decreases with increasing surface electronic density, enhancing electron donation from surface to pyridyl ring., (© 2021 Wiley-VCH GmbH.)

Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Gene Expression Omnibus database and StarBase were used to predict important regulatory pathways related to HCC. Then, the expression of KDM5B and microRNA-448 (miR-448) in HCC tissues was detected by RT-qPCR and Western blot analysis. The correlation between KDM5B and miR-448 expression was analysed by Pearson's correlation coefficient and ChIP experiments, and the targeting of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) by miR-448 was examined by luciferase assay. Additionally, the effect of KDM5B on the proliferation, migration, invasion and apoptosis as well as tumorigenicity of transfected cells was assessed using ectopic expression and depletion experiments. KDM5B was highly expressed in HCC cells and was inversely related to miR-448 expression. KDM5B demethylated H3K4me3 on the miR-448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. Our study uncovered that KDM5B regulates the YTHDF3/ITGA6 axis by inhibiting the expression of miR-448 to promote the occurrence of HCC., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Rationale: Significant concerns about the adverse effects following chimeric antigen receptor T cell (CAR-T) therapy are still remained including cytokine release syndrome (CRS). In rare circumstances, CRS may be refractory to tocilizumab and/or corticosteroids, a new treatment is needed for the management of CRS., Patient Concerns: We present a case of a 20-year-old male patient with acute lymphoblastic leukemia developed CRS after CD19/CD22 bispecific CAR-T treatment., Diagnosis: The patient was diagnosed with BCR-ABL(P210) positive B-ALL and developed CRS after CD19/CD22 bispecific CAR-T treatment., Interventions: Tocilizumab and methylprednisolone were administered, unfortunately the patient's symptoms of CRS were still not resolved. Another methylprednisolone and ruxolitinib were administered., Outcomes: The persistent fever and hypotension of this patient achieved a rapid clinical remission within hours after ruxolitinib administration., Lessons: Ruxolitinib can be used as an alternative therapeutic approach for severe and refractory CRS without impairing CAR-T amplification and anti-tumor effect., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the clinical effect of wheat grain moxibustion and warming acupuncture on chronic superficial gastritis of spleen-stomach deficiency and cold., Methods: A total of 200 patients with chronic superficial gastritis of spleen-stomach deficiency and cold were randomly divided into a wheat grain moxibustion group (100 cases, 13 cases dropped off ) and a warming acupuncture group (100 cases, 16 cases dropped off ). The acupoints of Zhongwan (CV 12), Tianshu (ST 25), Qihai (CV 6), Liangqiu (ST 34) and Zusanli (ST 36) were selected in both groups. The patients in the wheat grain moxibustion group were treated with wheat grain moxibustion, and 5 cone were given on every acupoint each time. Moxibustion was performed after acupuncture in the warming acupuncture group, and 3 cone each acupoint. Both groups were treated every other day for 15 times. The scores of clinical symptoms and signs, scores of physical component summary (PCS) and mental component summary (MCS) of quality of life in the two groups were recorded before and after treatment and during follow-up 1 month after treatment, and the clinical effects of the two groups were evaluated after treatment and during follow-up., Results: After treatment and during follow-up, the scores of clinical symptoms and signs of the two groups were lower than before treatment ( P <0.05), and the scores of PCS and MCS of quality of life were higher than before treatment ( P <0.05). At follow-up, the score of clinical symptoms and signs in the wheat grain moxibustion group was lower than that in the warming acupuncture group ( P <0.01), and the scores of PCS and MCS of quality of life were higher than those in the warming acupuncture group ( P <0.001). The total effective rate of the wheat grain moxibustion group was 93.1% (81/87), which was higher than 82.1% (69/84) of the warming acupuncture group at follow-up ( P <0.001)., Conclusion: The wheat grain moxibustion can effectively improve the clinical symptoms, signs and quality of life in patients with chronic superficial gastritis of spleen-stomach deficiency and cold, and its long-term effect is better than warming acupuncture.

A facile method for the preparation of 2,3-dialkyl-substituted quinazolinones from readily available N -arylamides and commercial isocyanates was developed. This one-pot procedure involves the chemoselective activation of the secondary amide with Tf 2 O/2-Br-Pyr, the sequential addition of isocyanate, and cyclization. The mild reaction is general for a wide range of substrates and can be run on a gram scale.

Acute myelogenous leukemia (AML) is the most common acute leukemia in adults. Despite great progress has been made in this field, the pathogenesis of AML is still not fully understood. We report here the biological role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in the pathogenesis of AML and the underlying mechanisms. The results showed that lncRNA SNHG5 was highly expressed in AML cancer cell lines. In vitro studies displayed that inhibition of SNHG5 with shRNA resulted in suppression of survival, cell cycle progression, migration/invasion of AML and capacity of adhesion and angiogenesis in human umbilical vein endothelial cells. Mechanistic studies revealed a SNHG5/miR-26b/connective tissue growth factor (CTGF)/vascular endothelial growth factor A (VEGFA) axis in the regulation of AML angiogenesis. Finally, Yin Yang 1 (YY1) was found to transactivate and interact with SNHG5 promoter, leading to the upregulation of SNHG5 in AML. Collectively, upregulation of lncRNA SNHG5 mediated by YY1, activates CTGF/VEGFA via targeting miR-26b to regulate angiogenesis of AML. Our work provides new insights into the molecular mechanisms of AML.

Fabricating single-molecule junctions with asymmetric metal electrodes is significant for realizing single-molecule diodes, but it remains a big challenge. Herein, we develop a z-piezo pulse-modulated scanning tunneling microscopy break junction (STM-BJ) technique to construct a robust asymmetric junction with different metal electrodes. The asymmetric Ag/BPY-EE/Au single-molecule junctions exhibit a middle conductance value in between those of the two individual symmetric metal electrode junctions, which is consistent with the order of calculated energy-dependent transmission coefficient T ( E ) of the asymmetric junctions at E F . Furthermore, the single-molecule conductance of Ag/BPY-EE/Au decreases by about 70% when reversing the bias voltage from 100 to -100 mV, and a clear asymmetric I - V feature at the single-molecule level is observed for these junctions. This rectifying behavior could be ascribed to a different interfacial coupling of molecules at the two end electrodes, which is confirmed by the different displacement of T ( E ) at the two bias voltages. Other asymmetric junctions exhibit similar rectifying behavior. The current work provides a feasible way to fabricate hybrid junctions based on asymmetric metal electrodes and investigate their electron transport toward the design of molecular rectifiers.

Objective: The moisture content in the soil directly affects the yield and quality of Panax notoginseng, especially at the age of three years old. However, the suitable moisture for the growth of P. notoginseng is unknown. In this study, the effects of different soil moisture on the growth of P. notoginseng were studied., Methods: Four different water treatments (0.45 field capacity (FC), 0.60 FC, 0.70 FC, and 0.85 FC) were set up in Shilin County, Yunnan Province, China. The water consumption and daily dynamic of water consumption were determined daily (from April 21 to October 18, 2012), and the daily dynamic of water consumption under different weather conditions (sunny and rainy) was determined. The transpiration coefficient and water use efficiency were calculated through dry matter accumulation and total water consumption. Accumulation of saponins of roots of P. notoginseng were analyzed by HPLC after treated, and the soil moisture content suitable for the growth of P. notoginseng was estimated by regression fitting of the active ingredient accumulation and the soil moisture content., Results: The water consumption of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.89, 3.68, 3.37 and 2.73 kg/plant per day, respectively. The water consumption of P. notoginseng from June to August was greater than other months. The daily dynamic of water consumption on sunny days and sunny days after rain showed a "double peak" feature, and it showed a "single peak" feature on rainy days. The water uses efficiency (WUE) of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.51, 3.32, 4.59, 3.39 gDW/kg H 2 O, respectively. The increase of soil moisture content would reduce the WUE of P. notoginseng . With the increase of soil water content, the content of notoginsenoside R 1 and ginsenoside Rg 1 did not change significantly, while the content of ginsenoside Rb 1 and Rd showed a decreasing trend., Conclusion: Soil moisture content significantly affected the water consumption of P. notoginseng , and when it was 56.4% of the maximum water holding capacity in the field, the sum of the four saponins of 100 strains of P. notoginseng was the highest., Competing Interests: The authors declare no conflict of interest., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Enhancing the gating performance of single-molecule conductance is significant for realizing molecular transistors. Herein, we report a new strategy to improve the electrochemical gating efficiency of single-molecule conductance with fused molecular structures consisting of heterocyclic rings of furan, thiophene, or selenophene. One order magnitude of gating ratio is achieved within a potential window of 1.2 V for the selenophene-based molecule, which is significantly greater than that of other heterocyclic and benzene ring molecules. This is caused by the different electronic structures of heterocyclic molecules and transmission coefficients T ( E ), and preliminary resonance tunneling is achieved through the highest occupied molecular orbital at high potential. The current work experimentally shows that electrochemical gating performance can be significantly modulated by the alignment of the conducting orbital of the heterocyclic molecule relative to the metal Fermi energy.

Diabetes is a group of metabolic disorders with an increased risk of developing cognitive impairment and dementia. The hippocampus in the forebrain contains an abundance of insulin receptors related to cognitive function and plays an important role in the pathophysiology of neurodegenerative disorders. Berberine from traditional Chinese medicine has been used to treat diabetes and diabetic cognitive impairment, although its related mechanisms are largely unknown. In this study, a STZ diabetes rat model feeding with a high-fat diet was used to test the effects of berberine compared with metformin. Oral glucose tolerance and hyperinsulinemic-euglycemic clamp were used for glucose metabolism and insulin resistance. The Morris water maze was used to observe the compound effects on cognitive impairment. Serum and hippocampal [Formula: see text]-amyloid peptide (A[Formula: see text], Tau and phosphorylated Tau protein deposition in the hippocampi were measured. The TUNEL assay was used to detect the neuronal apoptosis, supported by histomorphological changes and transmissional electron microscopy (TEM) image. Our data showed that the diabetic rats had a significantly cognitive impairment. In addition to improving glucose metabolism and reducing insulin resistance, berberine significantly improved the cognitive function in the rat. Berberine also effectively decreased the expression of hippocampal tau protein, phosphorylated Tau, and increased insulin receptor antibodies. Moreover, berberine downregulated the abnormal phosphorylation of A[Formula: see text] and Tau protein and improved hippocampal insulin signaling. The TUNEL assay confirmed that berberine reduced hippocampal neuronal apoptosis supported by TEM. Thus, berberine significantly improved the cognitive function in diabetic rats by changing the peripheral and central insulin resistance. The reduction of neuronal injury, A[Formula: see text] deposition, abnormal phosphorylation of Tau protein, and neuronal apoptosis in the hippocampus were observed as the related mechanisms of action.