Chemical and spatial dual-confinement engineering for stable Na-S batteries with approximately 100% capacity retention.

Sodium-sulfur (Na-S) batteries are attracting intensive attention due to the merits like high energy and low cost, while the poor stability of sulfur cathode limits the further development. Here, we report a chemical and spatial dual-confinement approach to improve the stability of Na-S batteries. It refers to covalently bond sulfur to carbon at forms of C-S/N-C=S bonds with high strength for locking sulfur. Meanwhile, sulfur is examined to be S1-S2 small species produced by thermally cutting S8 large molecules followed by sealing in the confined pores of carbon materials. Hence, the sulfur cathode achieves a good stability of maintaining a high-capacity retention of 97.64% after 1000 cycles. Experimental and theoretical results show that Na+ is hosted via a coordination structure (N···Na···S) without breaking the C-S bond, thus impeding the formation and dissolution of sodium polysulfide to ensure a good cycling stability. This work provides a promising method for addressing the S-triggered stability problem of Na-S batteries and other S-based batteries.

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA.

BACKGROUND: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed. METHODS: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTS: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively. CONCLUSIONS: Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).

Ultralong Bistable, Electrolytic MnO2-Based, Electrochromic Battery Enabled by Porous, Low-Barrier, Hydroxylated TiO2 Interface.

Electrochromic (EC) battery technology shows great potential in future "zero-energy building" by controlling outdoor solar transmission to tune heat gain as well as storing the consumed energy to reuse across other building systems. However, challenges still exist in exploring an electrochemical system to satisfy requirements on both ultra-long optical memory (also called bistability) without continuous power supply and high energy density. Herein, an EC battery is proposed to demonstrate ultra-long bistability (>760 h) based on the reversible deposition and dissolution of manganese oxide (MnO2) without the addition of any mediators. A porous low-barrier hydroxylated titanium dioxide (TiO2) interface is incorporated to synergistically enrich Mn2+-affinity active sites for deposition and effectively reduce the electron transport barrier of MnO2 for dissolution, thereby significantly improving the reversibility, high optical modulation (60.2% at 400 nm), and energy density (352 mAh m-2). The modification strategy is also verified on the cathode-less button cells with a much higher average coulombic efficiency (99.9%) compared to the batteries without the porous hydroxylated TiO2 interface (74.6%). These achievements lay a foundation for advancements in both electrochromism and Zn-Mn aqueous batteries.

Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-Specific Membrane Antigen-Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-Center, Prospective, Single-Arm Trial.

PURPOSE: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. MATERIALS AND METHODS: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. RESULTS: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. CONCLUSIONS: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

Surface-enhanced Raman scattering based on noble metal nanoassemblies for detecting harmful substances in food.

Residues of harmful substances in food can severely damage human health. The content of these substances in food is generally low, making detection difficult. Surface-enhanced Raman scattering (SERS), based on noble metal nanomaterials, mainly gold (Au) and silver (Ag), has exhibited excellent capabilities for trace detection of various substances. Noble metal nanoassemblies, in particular, have extraordinary flexibility and tunable optical properties, which cannot be offered by single nanoparticles (NPs). These nanoassemblies, with their various morphologies synthesized using NPs through artificially induced self-assembly or template-driven preparation, can significantly enhance the local electric field and create "hot spots" due to the gaps between adjacent NPs. Consequently, the SERS properties of NPs become more prominent, leading to improved performance in the trace detection of various substances and detection limits that are considerably lower than the current relevant standards. Noble metal nanoassemblies show promising potential in ensuring food safety. This review discusses the synthesis methods and SERS properties of noble metal nanoassemblies and then concentrates on their application in detecting biotoxins, drug residues, illegal additives, and heavy metals. The study provides valuable references for further research into the application of nanoassemblies in food safety detection.

A density functional theory study on the mechanism of toluene from dimethylcyclopentane catalyzed by the [GaH]2+ active site of Ga-ZSM-5.

The ONIOM (ωb97xd/6-31G(d,p):pm6) method was used to study the reaction mechanism of dimethylcyclopentane to toluene by the [GaH]2+ active site of Ga-ZSM-5. The results showed that the rate-determining step in the dimethylcyclopentane aromatization process is the ring expansion process. Compared to those of methylcyclopentane to benzene (D. D. Zhang, H. Y. Liu, L. X. Ling, H. R. Zhang, R. G. Zhang, P. Liu and B. J. Wang, Phys. Chem. Chem. Phys., 2021, 23, 10988-11003.), the free energy barriers of dimethylcyclopentane to toluene are significantly decreased, indicating that toluene is easier to produce than benzene, which confirmed the experimental results that a higher proportion of toluene than benzene is produced in the MTA process.

Two heat shock cognate 70 genes involved in spermatogenesis regulate the male fertility of Zeugodacus cucurbitae, as potential targets for pest control.

The melon fly Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agricultural quarantine pest threatening fruit and vegetable production. Heat shock cognate 70 (Hsc70), which is a homolog of the heat shock protein 70 (Hsp70), was first discovered in mice testes and plays an important role in spermatogenesis. In this study, we identified and cloned five Hsc70 genes from melon fly, namely ZcHsc70_1/2/3/4/5. Phylogenetic analysis showed that these proteins are closely related to Hsc70s from other Diptera insects. Spatiotemporal expression analysis showed that ZcHsc70_1 and ZcHsc70_2 are highly expressed in Z. cucurbitae testes. Fluorescence in situ hybridization further demonstrated that ZcHsc70_1 and ZcHsc70_2 are expressed in the transformation and maturation regions of testes, respectively. Moreover, RNA interference-based suppression of ZcHsc70_1 or ZcHsc70_2 resulted in a significant decrease of 74.61% and 63.28% in egg hatchability, respectively. Suppression of ZcHsc70_1 expression delayed the transformation of sperm cells to mature sperms. Meanwhile, suppression of ZcHsc70_2 expression decreased both sperm cells and mature sperms by inhibiting the meiosis of spermatocytes. Our findings show that ZcHsc70_1/2 regulates spermatogenesis and further affects the male fertility in the melon fly, showing potential as targets for pest control in sterile insect technique by genetic manipulation of males.

[Mechanism of Butylphthalide in Treating Delayed Encephalopathy After Carbon Monoxide Poisoning Based on Activation of Microglia].

Objective To explore the mechanism of butylphthalide (NBP) in regulating microglia activation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized into three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegetable oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-binding adapter molecule 1 (IBA1) was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA. Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency (P=0.001,P=0.029),reduced nerve cells (P=0.001,P=0.035),up-regulated expression of IBA1 (P=0.001,P=0.042),increased mean fluorescence intensity of IBA1 (P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α (TNF-α) (P=0.002,P=0.024),interleukin (IL)-6 (P=0.001,P=0.015),and IL-1ß (P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency (P=0.025),increased nerve cells (P=0.039),down-regulated expression of IBA1 (P=0.035),decreased average fluorescence intensity of IBA1 (P=0.031),and lowered levels of TNF-α (P=0.028),IL-6 (P=0.037),and IL-1ß (P=0.034). Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cognitive dysfunction and brain tissue damage caused by DEACMP.

Reversible Hydrogen Acceptor-Donor Enables Relay Mechanism for Nitrate-to-Ammonia Electrocatalysis.

Electrocatalytic nitrate reduction is a crucial process for sustainable ammonia production. However, to maximize ammonia yield efficiency, this technology inevitably operates at the potentials more negative than 0 V vs. RHE, leading to high energy consumption and competitive hydrogen evolution. To eradicate this issue, hydrogen tungsten bronze (HxWO3) as reversible hydrogen donor-acceptor is partnered with copper (Cu) to enable a relay mechanism at potentials positive than 0 V vs. RHE, which involves rapid intercalation of H into HxWO3 lattice, prompt de-intercalation of the lattice H and transfer onto Cu, and spontaneous H-mediated nitrate-to-ammonia conversion on Cu. The resulting catalysts demonstrated a high ammonia yield rate of 3332.9±34.1 mmol gcat-1 h-1 and a Faraday efficiency of ~100 % at 0.10 V vs. RHE, displaying a record-low estimated energy consumption of 17.6 kWh kgammonia-1. Using these catalysts, we achieve continuous ammonia production in an enlarged flow cell at a real energy consumption of 17.0 kWh kgammonia-1.

18 F-DCFPyL positron emission tomography/magnetic resonance imaging-guided ultrasound fusion biopsy is an identical pathway in prostate cancer diagnosis.

BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.

Partial Sulphidation to Regulate Coordination Structure of Single Nickel Atoms on Graphitic Carbon Nitride for Efficient Solar H2 Evolution.

To develop a non-precious highly efficient cocatalyst to replace Pt on graphitic carbon nitride (g-C3 N4 ) for solar H2 production is great significant, but still remains a huge challenge. The emerging single-atom catalyst presents a promising strategy for developing highly efficient non-precious cocatalyst owing to its unique adjustability of local coordination environment and electronic structure. Herein, this work presents a facile approach to achieve single Ni sites (Ni1 -N2 S) with unique local coordination structure featuring one Ni atom coordinated with two nitrogen atoms and one sulfur atom, confirmed by high-angle annular dark-field scanning transmission electron microscopy, X-ray absorption spectroscopy, and density functional theory calculation. Thanks to the unique electron structure of Ni1 -N2 S sites, the 1095 µmol g-1 h-1 of high H2 evolution rate with 4.1% of apparent quantum yield at 420 nm are achieved. This work paves a pathway for designing a highly efficient non-precious transition metal cocatalyst for photocatalytic H2 evolution.

Engineering CRISPR guide RNAs for programmable RNA sensors.

As the most valuable feature of the CRISPR system, the programmability based on Watson-Crick base pairing has been widely exploited in engineering RNA sensors. The base pairing in these systems offers a connection between the RNA of interest and the CRISPR effector, providing a highly specific mechanism for RNA detection both in vivo and in vitro. In the last decade, despite the many successful RNA sensing approaches developed during the era of CRISPR explosion, a deeper understanding of the characteristics of CRISPR systems and the continuous expansion of the CRISPR family members indicates that the CRISPR-based RNA sensor remains a promising area from which a variety of new functions and applications can be engineered. Here, we present a systematic overview of the various strategies of engineering CRISPR gRNA for programmable RNA detection with an aim to clarify the role of gRNA's programmability among the present limitations and future development of CRISPR-enabled RNA sensors.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Vesicoprostatic muscle reconstruction: a step further for immediate and early urinary continence.

OBJECTIVES: The vesicoprostatic muscle (VPM) is a longitudinal smooth muscle that originates from the trigone of the bladder or the opening of the ureter and is involved in urination as part of the detrusor apron. We explored the effect of VPM reconstruction on immediate and early recovery of urinary continence in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP). PATIENTS AND METHODS: A total of 523 patients with localized prostate cancer were enrolled from June 2018 to June 2020. All patients were diagnosed in our department based on magnetic resonance imaging and pathological findings on prostate biopsy. After 1:1 propensity score matching, 105 patient pairs were matched. The study was approved by our institutional review board and all surgeries were performed by three experienced high-volume surgeons. Demographic data, total operation time, pathological outcomes, the urinary continence rates of the two groups at different times after RALP, and factors influencing postoperative urinary continence after RALP were recorded. Student's t test was used to compare continuous variables and the Pearson χ2 test to compare categorical variables. Logistic regression analysis was used to identify factors affecting immediate and early postoperative urinary control. RESULTS: VPM reconstruction promoted immediate and early recovery of urinary continence (immediate continence, 66.67 vs. 40.00%, P = 0.000; 3-month continence, 80.95 vs. 64.76%, P = 0.008). CONCLUSIONS: VPM reconstruction improved immediate and early urinary continence in patients who underwent RALP.

Adrenocortical carcinoma with venous tumor invasion: is there a role for mini-invasive surgery?

OBJECTIVE: This study aims to investigate early oncologic outcomes in patients with adrenocortical carcinoma (ACC) with venous invasion (VI) treated using both open and mini-invasive approaches. PATIENTS AND MATERIALS: We conducted a retrospective analysis of 4 international referral center databases, including all the patients undergoing adrenalectomy for ACC with VI from January 2007 to March 2020. According to CT scan or MRI, the tumor thrombus was classified into four levels: (1) adrenal vein invasion; (2) renal vein invasion; (3) infra-hepatic Inferior vena cava (IVC); and (4) retro-hepatic IVC. In addition, we divided our patients into patients who had undergone open surgery and mini-invasive surgery. RESULTS: We identified 20 patients with a median follow-up of 12 months. The median tumor size was 110mm. ENSAT stage was II in 4 patients, III in 13 patients, and IV in 3 patients. Tumor thrombus extended in the adrenal vein (n=5), renal vein (n=1), infra-hepatic IVC (n=9), or into the retro-hepatic IVC (n=5). Ten patients were treated with a mini-invasive approach. The patient treated with an open approach reported a more aggressive disease. The two groups did not differ in surgical margins, surgical time, blood losses, complications, and length of stay. The prognosis resulted worse in the patient undergoing open. Kaplan-Meier analysis indicated a difference in OS for the patients stratified by ENSAT stage (Log-rank p=0.011); we also reported a difference in DFS for patients stratified for thrombus extension (p=0.004) and ENSAT stage (p<0.001). CONCLUSION: The DFS of patients with VI from ACC is influenced by the staging and the extension of the venous invasion; the staging influences the OS. The mini-invasive approach seems feasible in selected patients; however, further studies investigating the oncological outcomes are needed. A mini-invasive approach for adrenal tumors with venous invasion is an explorable option in very selected patients.

Comparison of freehand technique and a novel laser-guiding navigation system in femoral neck-cannulated screw fixation: a randomized controlled trial.

Cannulated screw fixation is essential in treating femoral neck fractures, and the widely used freehand technique has several limitations. Therefore, we designed a new laser-positioning and navigation system and compared its efficacy with that of the traditional freehand technique in the cannulated screw fixation of femoral neck fractures. This randomized controlled single-blind trial recruited patients with femoral neck fracture, who were treated using either the newly designed laser-navigation device or the freehand technique. In in-vitro experiments, using the femoral neck model, the laser group was better than the freehand group in terms of operation time (P = 0.0153) and radiation exposure time (P < 0.001). In in-vivo experiments, involving 30 patients (15 in each group), the laser group was better than the freehand group in terms of operation time (P < 0.001), radiation exposure time (P < 0.001), blood loss (P < 0.001) and first success rate (P = 0.03). There was no difference in visual analog scale score, Harris score, and fracture-healing time between the two groups. In conclusion, the novel laser-guiding navigation system resulted in shorter operation time, less radiation exposure, and higher first success rate compared with the freehand technique. Further qualified investigations with a larger number of patients and longer follow-up are required in the future.

GTSE1 promotes tumor growth and metastasis by attenuating of KLF4 expression in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors and is characterized by a poor prognosis. Although G2- and S -phase expressed-1 (GTSE1) is known to be involved in the progression and metastasis of various cancers, its significance and mechanism in ccRCC remain unknown. In the present study, we found that GTSE1 was overexpressed in ccRCC tissues, especially in metastatic samples. Moreover, high GTSE1 expression was positively correlated with higher pT stage, tumor size, clinical stage, and WHO/ISUP grade and worse prognosis. And GTSE1 expression served as an independent prognostic factor for overall survival (OS). In addition, GTSE1 knockdown inhibited ccRCC cell proliferation, migration, and invasion, and enhanced cell apoptosis in vitro and in vivo. GTSE1 was crucial for epithelial-mesenchymal transition (EMT) in ccRCC. Mechanistically, GTSE1 depletion could upregulate the expression of Krüppel-like factor 4 (KLF4), which acts as a tumor suppressor in ccRCC. Downregulation of KLF4 effectively rescued the inhibitory effect induced by GTSE1 knockdown and reversed the EMT process. Overall, our results revealed that GTSE1 served as an oncogene regulating EMT through KLF4 in ccRCC, and that GTSE1 could also serve as a novel prognostic biomarker and may represent a promising therapeutic target for ccRCC.

De Novo Design of the ArsR Regulated Pars Promoter Enables a Highly Sensitive Whole-Cell Biosensor for Arsenic Contamination.

Whole-cell biosensors for arsenic contamination are typically designed based on natural bacterial sensing systems, which are often limited by their poor performance for precisely tuning the genetic response to environmental stimuli. Promoter design remains one of the most important approaches to address such issues. Here, we use the arsenic-responsive ArsR-Pars regulation system from Escherichia coli MG1655 as the sensing element and coupled gfp or lacZ as the reporter gene to construct the genetic circuit for characterizing the refactored promoters. We first analyzed the ArsR binding site and a library of RNA polymerase binding sites to mine potential promoter sequences. A set of tightly regulated Pars promoters by ArsR was designed by placing the ArsR binding sites into the promoter's core region, and a novel promoter with maximal repression efficiency and optimal fold change was obtained. The fluorescence sensor PlacV-ParsOC2 constructed with the optimized ParsOC2 promoter showed a fold change of up to 63.80-fold (with green fluorescence visible to the naked eye) at 9.38 ppb arsenic, and the limit of detection was as low as 0.24 ppb. Further, the optimized colorimetric sensor PlacV-ParsOC2-lacZ with a linear response between 0 and 5 ppb was used to perform colorimetric reactions in 24-well plates combined with a smartphone application for the quantification of the arsenic level in groundwater. This study offers a new approach to improve the performance of bacterial sensing promoters and will facilitate the on-site application of arsenic whole-cell biosensors.

Step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus is the key to robot-assisted thrombectomy for Mayo III/IV tumor thrombus.

BACKGROUND: The surgical management of Mayo III/IV tumor thrombi is difficult and risky, and robotic surgery is even more difficult. The purpose of this study was to introduce the step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus, which was the core technique of robot operation for Mayo III/IV tumor thrombus. METHOD: A total of 18 patients were included in this study. The average tumor thrombus height was 2.4 cm above the level of the second porta hepatis (SPH), and 9 patients were prepared for cardiopulmonary bypass (CPB) before surgery. During the operation, the height of the tumor thrombus was lowered orderly for 2-3 times, and the blood flow blocking method was changed sequentially. The CPB was required when tumor thrombus in the atrium; After the height of the thrombus was lowered to the atrium entrance, CPB was stopped and the blood flow was blocked in the upper- and retro-hepatic inferior vena cava (IVC); After the tumor thrombus continued to descend to the lower part of the SPH, liver blood flow could be restored, and then, the blood flow was simply blocked in the retro-hepatic IVC to complete the removal of the thrombus and the repair or resection of the IVC. Finally, the diseased kidney and renal vein were removed. RESULTS: All operations were successfully completed, and 2 cases were transferred to laparotomy. Seven cases received CPB, while the other 11 did not. 15 patients underwent two times of the lowering of the tumor thrombus, 2 patients underwent one time and 1 patient underwent three times. The mean liver/IVC dissociation and vascular suspension time was 22.0 min. All patients had less than Clavien-Dindo grade III complications, no serious complications occurred during operation, and no patient died within 90 days. CONCLUSIONS: The step-by-step and orderly decline of tumor thrombus height is the key to the success of robot Mayo III / IV tumor thrombus surgery. This method can shorten FPH and CPB time and improve the success rate of surgery.

Targeted fluorescent imaging of a novel FITC-labeled PSMA ligand in prostate cancer.

In this study, we synthesized a novel fluorescein isothiocyanate (FITC)-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-FITC) via the Fmoc solid-phase synthesis method, and the application value of PSMA-FITC in targeted fluorescence imaging of PSMA-positive prostate cancer was evaluated. The PSMA ligand developed based on the Glu-urea-Lys structure was linked to FITC by aminocaproic acid (Ahx) to obtain PSMA-FITC. The new probe was evaluated in vitro and in vivo. Fluorescence microscopy examination of PSMA-FITC in PSMA(+) LNCaP cells, PSMA(-) PC3 cells, and blocked LNCaP cells showed that the binding of PSMA-FITC with PSMA was target-specific. For in vivo optical imaging, PSMA-FITC exhibited rapid 22Rv1 tumor targeting within 30 min of injection, and the highest tumor-background ratio (TBR) was observed 60 min after injection. The TBR was 3.45 ± 0.31 in the nonblocking group and 0.44 ± 0.13 in the blocking group, which was consistent with the in vitro results. PSMA-FITC is a promising probe and has important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to obtain accurate tumor images for radical prostatectomy.