[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

Incidence and severity of SARS-CoV-2 reinfection, a multicenter cohort study in Shanghai, China.

During March 2022 to January 2023, two Omicron waves hit Shanghai and caused a massive number of reinfections. To better understand the incidence and clinical characteristics of SARS-CoV-2 reinfection in Shanghai, China, we conducted a multicenter cohort study. COVID-19 patients first infected with BA.2 (March 1, 2022-May 23, 2022) who were quarantined in Huashan Hospital, Renji Hospital, and Shanghai Jing'an Central Hospital were followed up for reinfection from June 1, 2022 to January 31, 2023. Of 897 primary infections, 148 (16.5%) experienced reinfection. Incidence rate of reinfection was 0.66 cases per 1000 person-days. Female gender (adjusted odds ratio [aOR]= 2.19, 95% confidence interval [CI]: 1.29-3.83) was a risk factor for reinfection. The four most common symptoms of reinfections during the circulation of BA.5 sublineages were cough (62.59%), sore throat (54.42%), fatigue (48.98%), and fever (42.57%). Having received a booster vaccination was not associated with reduced severity of reinfection in comparison with not having received booster vaccination. After matched 1:1 by age and sex, we found that reinfections with BA.5 sublineages had significantly lower occurrence and severity of fever, fatigue, sore throat, and cough, as compared to primary infections with BA.5 sublineages. SARS-CoV-2 Omicron reinfections were less severe than Omicron primary infections during the circulation of the same subvariant. Protection offered by both vaccination and previous infection was poor against SARS-CoV-2 reinfection.

Complications after radiofrequency ablation of hyperparathyroidism secondary to chronic kidney disease.

OBJECTIVE: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). METHODS: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. RESULTS: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = -2.222; p = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p = .005), had more ablated nodules (p = .003) and higher blood phosphorus (p = .012) and alkaline phosphatase (ALP) levels (p = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. CONCLUSIONS: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.

Atomic Magnetometer Achieves Visual Salience Analysis in Drosophila.

An atomic magnetometer (AM) was used to non-invasively detect the tiny magnetic field generated by the brain of a single Drosophila. Combined with a visual stimulus system, the AM was used to study the relationship between visual salience and oscillatory activity of the Drosophila brain by analyzing changes in the magnetic field. Oscillatory activity of Drosophila in the 1-20 Hz frequency band was measured with a sensitivity of 20 fT/Hz. The field in the 20-30 Hz band under periodic light stimulation was used to explore the correlation between short-term memory and visual salience. Our method opens a new path to a more flexible method for the investigation of brain activity in Drosophila and other small insects.

An Integrated Single-Beam Three-Axis High-Sensitivity Magnetometer.

Three-axis atomic magnetometers have great advantages for interpreting information conveyed by magnetic fields. Here, we demonstrate a compact construction of a three-axis vector atomic magnetometer. The magnetometer is operated with a single laser beam and with a specially designed triangular 87Rb vapor cell (side length is 5 mm). The ability of three-axis measurement is realized by reflecting the light beam in the cell chamber under high pressure, so that the atoms before and after reflection are polarized along two different directions. It achieves a sensitivity of 40 fT/Hz in x-axis, 20 fT/Hz in y-axis, and 30 fT/Hz in z-axis under spin-exchange relaxation-free regime. The crosstalk effect between different axes is proven to be little in this configuration. The sensor configuration here is expected to form further values, especially for vector biomagnetism measurement, clinical diagnosis, and field source reconstruction.

Optical biosensor based on weak value amplification for the high sensitivity detection of Pertuzumab in combination with Trastuzumab binding to the extracellular domain of HER2.

A real-time optical phase sensing scheme based on weak value amplification was proposed to monitor the especially binding process of Pertuzumab combined with Trastuzumab on HER2 positive cells. From the wavelength shift of output spectrum, the phase difference between measuring and referential path related to the concentration of Pertuzumab as well as Trastuzumab could be calculated. With this approach, the limit of detection (LOD) of 5.54 × 10-13 M for Pertuzumab assay was achieved. Besides, the kinetics signal of Pertuzumab in combination with Trastuzumab binding to HER2 was detected in real time. Experimental results demonstrated that both Trastuzumab and Pertuzumab can be captured by HER2, but the former was significantly superior to the latter in terms of the target number. Additionally, the binding speed was analyzed and demonstrated to be closely correlated with the initial concentration of the targeting agents.

Exposing Cu(100) Surface via Ion-Implantation-Induced Oxidization and Etching for Promoting Hydrogen Evolution Reaction.

Metallic materials with unique surface structure have attracted much attention due to their unique physical and chemical properties. However, it is hard to prepare bulk metallic materials with special crystal faces, especially at the nanoscale. Herein, we report an efficient method to adjust the surface structure of a Cu plate which combines ion implantation technology with the oxidation-etching process. The large number of vacancies generated by ion implantation induced the electrochemical oxidation of several atomic layers in depth; after chemical etching, the Cu(100) planes were exposed on the surface of the Cu plate. As a catalyst for acid hydrogen evolution reaction, the Cu plate with (100) planes merely needs 273 mV to deliver a current density of 10 mA/cm2 because the high-energy (100) surface has moderate hydrogen adsorption and desorption capability. This work provides an appealing strategy to engineer the surface structure of bulk metallic materials and improve their catalytic properties.

Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer.

BACKGROUND: Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer. CASE PRESENTATION: AC1 A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported. DISCUSSION: For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.

Target-Triggered Assembly in a Nanopipette for Electrochemical Single-Cell Analysis.

Engineered nanopipette tools have recently emerged as a powerful approach for electrochemical nanosensing, which has major implications in both fundamental biological research and biomedical applications. Herein, we describe a generic method of target-triggered assembly of aptamers in a nanopipette for nanosensing, which is exemplified by sensitive and rapid electrochemical single-cell analysis of adenosine triphosphate (ATP), a ubiquitous energy source in life and important signaling molecules in many physiological processes. Specifically, a layer of thiolated aptamers is immobilized onto a Au-coated interior wall of a nanopipette tip. With backfilled pairing aptamers, the engineered nanopipette is then used for probing intracellular ATP via the ATP-dependent linkage of the split aptamers. Due to the higher surface charge density from the aptamer assembly, the nanosensor would exhibit an enhanced rectification signal. Besides, this ATP-responsive nanopipette tool possesses excellent selectivity and stability as well as high recyclability. This work provides a practical single-cell nanosensor capable of intracellular ATP analysis. More generally, integrated with other split recognition elements, the proposed mechanism could serve as a viable basis for addressing many other important biological species.

A Practical Electrochemical Nanotool for Facile Quantification of Amino Acids in Single Cell.

Though significant advances are made in the arena of single-cell electroanalysis, quantification of intracellular amino acids of human cells remains unsolved. Exemplified by l-histidine (l-His), this issue is addressed by a practical electrochemical nanotool synergizing the highly accessible nanopipette with commercially available synthetic DNAzyme. The fabricated nanotools are screened before operation of a single-use manner, and the l-His-provoked cleavage of the DNA molecules can be sensibly transduced by the ionic current rectification response, the intrinsic property of nanopipette governed by its interior surface charges. Regional distribution of cytosolic l-His level in human cells is electrochemically quantified for the first time, and time-dependent drug treatment effects are further revealed. This work unveils the possibility of electrochemistry for quantification of cytosolic amino acids of a spatial- and time-based manner and ultimately enables a better understanding of amino acid-involved events in living cells.

Quantification of HER2 in COS7 cells using quantum weak measurement.

A Mach-Zehnder interferometer system based on weak measurement was set up to determinate the concentration variation of molecule by measuring the phase difference change between the two optical paths. The spectrum of the light was recorded to monitor the concentration of trastuzumab (Herceptin), which is a humanised monoclonal antibody, targeted to human epidermal growth factor receptor 2 (HER2). The trastuzumab targeting to HER2 was real-time detected and continuously monitored, the HER2 numbers of COS7 cells on a coverslip was determined at pico-molar level. Our weak measurement enabled method proposes an alternative approach for the concentration detection of molecules, providing a promising functional tool for the quantification of HER2 in cancer cells, possibly promoting fields such as the diagnosis and treatment of cancer.

Hemostasis functions are associated with hemorrhagic transformation in non-atrial fibrillation patients: a case-control study.

BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.

Structural titration of receptor ion channel GLIC gating by HS-AFM.

Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated, cation-selective channel, is a prokaryotic homolog of the pentameric Cys-loop receptor ligand-gated ion channel family. Despite large changes in ion conductance, small conformational changes were detected in X-ray structures of detergent-solubilized GLIC at pH 4 (active/desensitized state) and pH 7 (closed state). Here, we used high-speed atomic force microscopy (HS-AFM) combined with a buffer exchange system to perform structural titration experiments to visualize GLIC gating at the single-molecule level under native conditions. Reference-free 2D classification revealed channels in multiple conformational states during pH gating. We find changes of protein-protein interactions so far elusive and conformational dynamics much larger than previously assumed. Asymmetric pentamers populate early stages of activation, which provides evidence for an intermediate preactivated state.

An Optical Chiral Sensor Based on Weak Measurement for the Real-Time Monitoring of Sucrose Hydrolysis.

A chiral sensor with optical rotation detection based on weak measurement for the kinetic study of sucrose hydrolysis is presented. Based on the polarization modulation to the pre-selection state, the optical rotation of chiral sample was accurately determined through the central wavelength shift of the output spectrum. With this approach, the concentration response curves of sucrose and its hydrolysis products, i.e., fructose and glucose, were experimentally obtained for the hydrolysis analysis. By collecting the output spectrum with a frequency of 100 Hz and fitting the central wavelength shift synchronously during the measurement, the sucrose hydrolysis process was monitored in real time. Different hydrolysis conditions with varied concentration of invertase enzyme and citrate were implemented in this work. As a consequence, the real-time hydrolysis curves of the hydrolysis process with distinct velocities was achieved and analyzed. Such a kinetic monitoring about sucrose hydrolysis with optical rotation detection technology played a critical role in the researches involving sucrose, and also revealed the great potential of weak measurement in intersections, such as food safety inspection and chemical analysis.

HDAC6 inhibitor, ACY1215 suppress the proliferation and induce apoptosis of gallbladder cancer cells and increased the chemotherapy effect of gemcitabine and oxaliplatin.

As an anti-tumor agent, histone deacetylases (HDACs) inhibitors have attracted wide attention. ACY1215 is a highly effective selective inhibitor of HDAC6, which can inhibit many kinds of tumors. Whether the expression of HDAC6 and its new inhibitor ACY1215 can inhibit the proliferation of gallbladder cancer cells and induce their apoptosis remains to be further studied. The purpose of this study was to explore the effects of ACY1215 on the gallbladder cancer cells. Cell proliferation of GBC-SD and SGC-996 was assessed by cell counting kit-8 assay and colony formation assay. Flow cytometry was used to detect the apoptosis of gallbladder cancer cells. Western blot was used to detect the expressions of PCNA，KI67, and apoptosis-related proteins of gallbladder cancer cells. The HDAC6 inhibitor ACY1215 suppressed the proliferation of GBC-SD and SDC-996 cells and promoted the apoptosis of gallbladder cancer cells. The HDAC6 inhibitor ACY1215 increases the chemotherapy effect of gemcitabine and oxaliplatin. ACY1215 could suppress cell proliferation and induce apoptosis of GBC-SD and SGC-996, and increased the chemotherapy effect of gemcitabine and oxaliplatin, which provides a rationale for the combination of HDAC6 selective inhibitors with other anticancer agents in treating gallbladder cancer.

An Integrated Electrochemical Nanodevice for Intracellular RNA Collection and Detection in Single Living Cell.

New tools for single-cell interrogation enable deeper understanding of cellular heterogeneity and associated cellular behaviors and functions. Information of RNA expression in single cell could contribute to our knowledge of the genetic regulatory circuits and molecular mechanism of disease development. Although significant progresses have been made for intracellular RNA analysis, existing methods have a trade-off between operational complexity and practical feasibility. We address this challenge by combining the ionic current rectification property of nanopipette reactor with duplex-specific nuclease-assisted hybridization chain reaction for signal amplification to realize a simple and practical intracellular nanosensor with minimal invasiveness, which enables single-cell collection and electrochemical detection of intracellular RNA with cell-context preservation. Systematic studies on differentiation of oncogenic miR-10b expression levels in non-malignant breast cells, metastatic breast cancer cells as well as non-metastatic breast cancer cells were then realized by this nanotool accompanied by assessment of different drugs effects. This work has unveiled the ability of electrochemistry to probe intracellular RNA and opened new opportunities to study the gene expression and heterogeneous complexity under physiological conditions down to single-cell level.

An Integrated Photoelectrochemical Nanotool for Intracellular Drug Delivery and Evaluation of Treatment Effect.

With reduced background and high sensitivity, photoelectrochemistry (PEC) may be applied as an intracellular nanotool and open a new technological direction of single-cell study. Nevertheless, the present palette of single-cell tools lacks such a PEC-oriented solution. Here a dual-functional photocathodic single-cell nanotool capable of direct electroosmotic intracellular drug delivery and evaluation of oxidative stress is devised by engineering a target-specific organic molecule/NiO/Ni film at the tip of a nanopipette. Specifically, the organic molecule probe serves simultaneously as the biorecognition element and sensitizer to synergize with p-type NiO. Upon intracellular delivery at picoliter level, the oxidative stress effect will cause structural change of the organic probe, switching its optical absorption and altering the cathodic response. This work has revealed the potential of PEC single-cell nanotool and extended the boundary of current single-cell electroanalysis.

LncRNA Gm4419 induces cell apoptosis in hepatic ischemia-reperfusion injury via regulating the miR-455-SOX6 axis.

Long non-coding RNA (lncRNA) is known to be involved in a variety of diseases. However, the role of Gm4419 in hepatic ischemia-reperfusion (I/R) injury remains unknown. To study this, we first established a rat model of hepatic I/R, and a BRL-3A cell model of hypoxia-reoxygenation (H/R) for in vivo and in vitro studies. Staining with hematoxylin and eosin and hepatic injury scores were used to evaluate the degree of hepatic I/R injury. Cell apoptosis was assessed via staining with Edu, and with annexin V-FITC-propidium iodide assays. The interactions between Gm4419 and miR-455, as well as miR-455 and SOX6 were evaluated via luciferase reporter activity assays and RNA immunoprecipitation assays. In vivo, we found that Gm4419 was up-regulated in the rats subjected to I/R. Moreover, knockdown of Gm4419 alleviated the I/R-induced liver damage in the rats. In vitro, knockdown of Gm4419 alleviated H/R-induced apoptosis in BRL-3A cells. Interestingly, we found that miR-455 is a target of Gm4419, and Gm4419 regulates the expression of miR-455 via sponging. Furthermore, SOX6 was proven to be the target of miR-455. Finally, rescue experiments confirmed that knockdown of Gm4419 inhibits apoptosis by regulating miR-455 and SOX6 in H/R-treated BRL-3A cells. Therefore, our findings show that the lncRNA Gm4419 accelerates hepatic I/R injury by targeting the miR-455-SOX6 axis, which suggests a novel therapeutic target for hepatic I/R injury.

Sleep quality and military training injury during basic combat training: a prospective cohort study of Chinese male recruits.

OBJECTIVE: To examine the association between sleep quality and military training injury (MTI) in recruits during basic combat training (BCT). METHODS: Participants were new recruits undergoing 12-week military BCT in China. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI) . Participants were classified into two groups based on their sleep quality (group 1, good sleep, PSQI score <7; group 2, poor sleep, PSQI score ≥7) at the start of BCT. Logistic regression analysis was conducted to test whether baseline PSQI score was associated with MTI incidence during BCT. RESULTS: A total of 563 participants were included. The incidence of MTI was significantly lower in group 1 (48/203, 23.6%) than in group 2 (150/360, 41.7%) (p<0.001). Logistic regression analysis showed that the odds of MTI were 2.307 times higher in group 2 than in group 1 without adjusting for confounders: OR=2.307, p<0.001. When the model was adjusted for age, ethnicity, educational level and family income (OR=2.285) or for the previous confounders plus body mass index (OR=2.377), the results were similar (both p<0.001). Analysis of the types of initial MTI showed that group 2 had about 2.1 times higher odds of soft tissue injury than group 1 (p<0.001 in all the three models). CONCLUSION: Sleep quality before BCT influences the incidence of MTI, especially of soft tissue injury.

Design of a reconfigurable broadband greyscale multiplexed metasurface hologram.

Holograms are a promising state-of-the-art technique that are able to reproduce fully three-dimensional images. However, most elementary holograms only recover a nonadjustable image restricted by a certain amplitude and phase. Recently, the concept of the reconfigurable metasurface has come into sight. The reconfigurable metasurfaces can be tuned dynamically through a physics control signal from outside. Here we design and realize a series of novel, to the best of our knowledge, reconfigurable metasurfaces. Using these devices, an advanced metasurface hologram effect could be easier to achieve. Moreover, the reconfigurable property of such tunable metasurface enables independent control of advanced multiplexed channel functionalities to exist in comparison with the conventional static metasurface holograms. Our method creates unprecedented display and virtual effects, and it opens a novel way to a more flexible methodology of dynamic control of electromagnetic waves.