The metabolic slowdown caused by the deletion of pspA accelerates protein aggregation during stationary phase facilitating antibiotic persistence.

Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A (pspA) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA. Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA. This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

Optimal parameter selection for the THz-CCS system based on an incoherent light source.

Terahertz cross correlation spectroscopy (THz-CCS) systems using broadband incoherent light as the pumping source have received increasing attention from researchers in recent years. However, a comprehensive and in-depth understanding of THz-CCS is still needed to obtain a detailed optimization scheme. Here we systematically investigate the influences of the detection parameters, light propagation process, and pump source on the CCS signals. The impacts of the filter slopes and time constants in lock-in detection are revealed for optimizing the signal-to-noise ratio and bandwidth of the THz signal. By varying the optical fiber length and dispersion coefficient, the dispersion insensitivity of THz-CCS was experimentally demonstrated. The comparison of different pump sources (SLD and ASE) shows that the over-wide and non-flat pump spectrum may attenuate the CCS signal because of the energy waste brought by the photomixing process under the limited bandwidth of the photomixer. Our research may lead to a deeper understanding and further optimization of the THz-CCS system, which will promote the development and widespread application of what is to the best of our knowledge a new technique.

Clinical manifestations, antimicrobial resistance and genomic feature analysis of multidrug-resistant Elizabethkingia strains.

BACKGROUND: Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. METHODS: Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. RESULTS: The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five ß-lactamase genes (blaGOB, blaBlaB, blaCME, blaOXA, and blaTEM) responsible for ß-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that "metabolism" constituted the largest category within the core genome, while "information storage and processing" was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (ß-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. CONCLUSION: The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

Vitamin C, vitamin E, ß-carotene and risk of Parkinson's disease: a systematic review and dose-response meta-analysis of observational studies.

OBJECTIVE: This study aimed to explore the relationship between the intake of vitamin C, vitamin E and ß-carotene, and the risk of Parkinson's disease (PD). METHODS: Web of Science, Embase, PubMed, Cochrane library, CNKI, and WanFang databases were searched from inception to 29 August 2022 for observational studies reporting the odds ratios (ORs) or relative risks (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by Vitamin C/Vitamin E/ß-carotene intake. Random-effects models, publication bias assessment, subgroup, sensitivity and dose-response analyses were performed, using.Stata version 12.0. RESULTS: A total of 13 studies were included. There was no significant association between high-dose vitamin C intake and the risk of PD compared with low-dose vitamin C intake (RR = 0.98, 95%CI:0.89,1.08). Compared with low-dose intake, high-dose intake of vitamin E can prevent the risk of PD (RR = 0.87, 95%CI:0.77,0.99). Compared with lower ß-carotene intake, there was a borderline non-significant correlation between higher intake and PD risk (RR = 0.91, 95%CI:0.82,1.01), and high dose ß-carotene intake was found to be associated with a lower risk of PD in women (RR = 0.78, 95%CI:0.64,0.96). CONCLUSION: This study shows that vitamin E intake can reduce the risk of PD and play a preventive role.

An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

Tetrahedral DNA-linked aptamer-antibody-based sandwich-type electrochemical sensor with Ag@Au core-shell nanoparticles as a signal amplifier for highly sensitive detection of α-fetoprotein.

The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (Ti3C2TX)-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing H2O2 reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by H2O2 reduction increased linearly with the logarithm of AFP concentration from 5 × 10-4 ng/mL to 1 × 105 ng/mL, accompanied by a low detection limit (1.6 × 10-4 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis.

[Carbapenemase Genes, Virulence Genes, and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Derived From Bloodstream Infections]. / è¡€æµæ„ŸæŸ“ç¢³é’éœ‰çƒ¯è€è¯è‚ºç‚Žå ‹é›·ä¼¯èŒçš„è€è¯åŸºå› å’Œæ¯’åŠ›åŸºå› åŠåˆ†å­æµè¡Œç— å­¦ç ”ç©¶.

Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China. Methods: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentration (MIC) was determined by microbroth dilution method. The common carbapenemase resistant genes and virulence factors were identified by PCR. Homology analysis was performed by multilocus sequencing typing. Whole genome sequencing was performed to analyze the genomic characteristics of CRKP without carbapenemase. Results: The 131 strains of CRKP showed resistance to common antibiotics, except for polymyxin B (1.6% resistance rate) and tigacycline (8.0% resistance rate). A total of 105 (80.2%) CRKP strains carried the Klebsiella pneumoniae carbapenemase (KPC) resistance gene, 15 (11.4%) strains carried the New Delhi Metallo-ß-lactamase (NDM) gene, and 4 (3.1%) isolates carried both KPC and NDM genes. Sequence typing (ST) 11 (74.0%) was the dominant sequence type. High detection rates for mrkD (96.2%), fimH (98.5%), entB (100%), and other virulence genes were reported. One hypervirulent CRKP strain was detected. The seven strains of CRKP that did not produce carbapenemase were shown to carry ESBL or AmpC genes and had anomalies in membrane porins OMPK35 and OMPK36, according to whole genome sequencing. Conclusion: In a large-scale tertiary-care general hospital, CRKP mainly carries the KPC gene, has a high drug resistance rate to a variety of antibiotics, and possesses multiple virulence genes. Attention should be paid to CRKP strains with high virulence.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

A positive feedback circuit driven by m6A-modified circular RNA facilitates colorectal cancer liver metastasis.

BACKGROUND: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. METHODS: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. RESULTS: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. CONCLUSIONS: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Evaluation of the Autof ms1000 mass spectrometry for rapid clinical identification of filamentous fungi.

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized microbial identification. However, there is a lack of data on its performance in identifying filamentous fungi. The objective of our study was to evaluate the accuracy of the Autof ms1000 mass spectrometry for identifying filamentous fungi in the clinical microbiology laboratory. RESULTS: Among 106 samples tested using the Autof ms1000 system, 101 (95.28%) were identified at the genus or species level, and 81 (76.41%) were accurately identified at the species level. Additionally, we developed a new rapid formic acid extraction method with simple pretreatment for filamentous fungi that saved time and provided accurate results. CONCLUSIONS: The Autof ms1000 mass spectrometer proved to be a valuable tool for identifying filamentous fungi. However, upgrading the database is recommended for correctly identifying rare strains.

Association of MPPED2 gene variant rs10767873 with kidney function and risk of cardiovascular disease in patients with hypertension.

Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (ß = 0.041, p = 0.01) and lower levels of serum creatinine (ß = -0.068, p = 0.001) and serum uric acid (ß = -0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.

Thickness-dependent loss-induced failure of an ideal ENZ-enhanced optical response in planar ultrathin transparent conducting oxide films.

Ultrathin planar transparent conducting oxide (TCO) films are commonly used to enhance the optical response of epsilon-near-zero (ENZ) devices; however, our results suggest that thickness-dependent loss renders them ineffective. Here, we investigated the thickness-dependent loss of indium tin oxide (ITO) films and their effect on the ENZ-enhanced optical responses of ITO and ITO/SiO2 multilayer stacks. The experimental and computational results show that the optical loss of ITO films increases from 0.47 to 0.70 as the thickness decreases from 235 to 52 nm, which results in a reduction of 60% and 45% in the maximum field enhancement factor of a 52-nm monolayer ITO and 4-layer ITO/SiO2 multilayer stack, respectively. The experimental results show that the ENZ-enhanced nonlinear absorption coefficient of the 52-nm single-layer ITO film is -1.6 × 103 cm GW-1, which is 81% lower than that of the 235-nm ITO film (-8.6 × 103 cm GW-1), indicating that the thickness-dependent loss makes the ultrathin TCO films unable to obtain greater nonlinear responses. In addition, the increased loss reduces the cascading Berreman transmission valley intensity of the 4-layer ITO/SiO2 multilayer stack, resulting in a 42% reduction in the ENZ-enhanced nonlinear absorption coefficient compared to the 235-nm ITO film and a faster hot electron relaxation time. Our results suggest that the thickness and loss trade-off is an intrinsic property of TCO films and that the low-loss ultrathin TCO films are the key to the robust design and fabrication of novel ENZ devices based on flat ultrathin TCO films.

Establishment of a new prognostic risk model of GNG7 pathway-related molecules in clear cell renal cell carcinoma based on immunomodulators.

Clear cell renal cell carcinoma (CCRCC) is a common tumor of the urological system for which surgery is the preferred treatment, but there is a lack of therapeutic options after surgery. This study aims to explore the biological role of GNG7 on CCRCC from a genetic perspective. Differences in mRNA expression and patient survival of GNG7 in patients with CCRCC and healthy patients were analyzed using the TCGA database. It was observed that GNG7 gene expression was downregulated in CCRCC tissue compared with healthy tissue, and high GNG7 predicted better prognosis for patients, and GNG7 also showed strong variability in clinical and TMN staging. The immune relevance of GNG7 and related genes was explored using renal cancer data from CCLE and TISIDB database. It was verified that the risk score constructed by 7 GNG7-related regulators might be used as an independent prognostic risk factor for CCRCC. A CCRCC prognostic model that involved 7 immune genes was further established to predict the survival probabilities of patients. At last, the GEO database and immunochemical tissue staining were used to validate GNG7 expression in CCRCC. Our study proposed a novel panel of genes to predict CCRCC OS based on GNG7-related immune genes, which may help to accurately predict the prognosis of CCRCC patients and make better clinical decisions for individual treatment.

Lymphovascular invasion represents a superior prognostic and predictive pathological factor of the duration of adjuvant chemotherapy for stage III colon cancer patients.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) can indicate poor survival outcomes in colorectal cancer, but few studies have focused on stage III colon cancer. The current study aimed to confirm the prognostic value of LVI and PNI and identify patients who could benefit from a complete duration of adjuvant chemotherapy based on the two pathological factors. METHODS: We enrolled 402 consecutive patients with stage III colon cancer who received colon tumor resection from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Survival analyses were performed by using Kaplan-Meier method with log-rank tests. Risk factors related to disease-free survival (DFS) and overall survival (OS) were identified through Cox proportional hazards analysis. RESULTS: 141 (35.1%) patients presented with LVI, and 108 (26.9%) patients with PNI. The LVI-positive group was associated with poorer 3-year DFS (86.5% vs. 76.3%, P = 0.001) and OS (96.0% vs. 89.1%, P = 0.003) rates compared with the LVI-negative group. The PNI-positive group showed a worse outcome compared with the PNI-negative group in 3-year DFS rate (72.5% vs. 86.7%, P < 0.001). Moreover, LVI-positive group present better 3-year DFS and OS rate in patients completing 6-8 cycles of adjuvant chemotherapy than those less than 6 cycles (3-year DFS: 80.0% vs. 64.9%, P = 0.019; 3-year OS: 93.2% vs. 76.3%, P = 0.002). CONCLUSIONS: LVI is a superior prognostic factor to PNI in stage III colon cancer patients undergoing curative treatment. PNI status can noly predict the 3-year DFS wihout affecting the 3-year OS. Furthermore, LVI also represents an effective indicator for adjuvant chemotherapy duration.

Water hydration of polyethylene glycol dimethyl ether.

In this work, GHz and THz complex dielectric spectra of a polyethylene glycol dimethyl ether (2000 g/mol) aqueous solution were studied. The reorientation relaxation of water in this kind of macro-amphiphilic molecule solution can be well described by three Debye models, including under-coordinated water, bulk-like water [water molecules in a tetrahedral hydrogen bond network (bulk water) and bulk water molecules affected by hydrophobic groups], and slow hydrating water (water molecules donating hydrogen bonds to hydrophilic ether groups). The reorientation relaxation timescales of bulk-like water and slow hydration water both show increases with concentration from 9.8 to 26.7 ps and from 46.9 to 100.1 ps, respectively. By estimating the ratios of the dipole moment of slow hydration water to the dipole moment of bulk-like water, we calculated the experimental Kirkwood factors of bulk-like and slow hydrating water. The experimental Kirkwood factor of bulk-like water increased from 3.17 to 3.44 with concentrations, while the experimental Kirkwood factor of slow hydrating water roughly remained constant at 4.13 from concentrations of 15%-60%. The estimated water molecule numbers of three water components around monomers also confirm our sorting for water components.

NEDD4L inhibits migration, invasion, cisplatin resistance and promotes apoptosis of bladder cancer cells by inactivating the p62/Keap1/Nrf2 pathway.

PURPOSE: This study identified the function of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) on bladder cancer (BLCA). METHODS: NEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit-8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP-resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models. RESULTS: The down-regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP-resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 µM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up-regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP-resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA. CONCLUSION: NEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment.

Rationally Designed Fluorinated Amide Additive Enables the Stable Operation of Lithium Metal Batteries by Regulating the Interfacial Chemistry.

A fluorinated amide molecule with two functional segments, namely, an amide group with a high donor number to bind lithium ions and a fluorine chain to expel carbonate solvents and mediate the formation of LiF, was designed to regulate the interfacial chemistry. As expected, the additive preferably appears in the first solvation sheath of lithium ions and is electrochemically reduced on the anode, and thus an inorganic-rich solid electrolyte interphase is generated. The morphology of deposited lithium metal evolves from brittle dendrites into a granular shape. Consequently, the Li||LiFePO4 cell shows an excellent capacity retention of 92.7% at a high rate of 5 C after 800 cycles. Besides, the Li||LiNi0.8Co0.1Mn0.1O2 cell succeeds to maintain 98.1% of the initial capacity after 100 cycles at 1 C. Our designing of N,N-diethyl- 2,3,3,3-tetrafluoropropionamide (denoted as DETFP) highlights the importance of a "high donor number" and may shed light on the design principles of electrolytes for high performance batteries.

Sonosensitive Phase-Changeable Nanoparticle Mediated Enhanced Chemotherapy in Prostate Cancer by Low-Intensity Focused Ultrasound.

Prostate cancer (PCa) is one of the most common cancer types. Early detection of PC offers the best chance of successful treatment. A noninvasive, image-guided therapy mediated by targeted nanoparticles (NPs) has the potential to improve the efficacy and safety of cancer therapies. Herein, we report a sonosensitive nanoparticle modified with anti-PSMA (prostate-specific membrane antigen) antibodies to activate target prostate tumors. These nanoparticles (PFP@IR780@PTX@liposome NPs) were co-loaded with the chemotherapeutic agent docetaxel and the sonosensitizer IR780, as well as phase-changeable perfluorocarbon (PFC) liquids. The liquid-gas phase change could be induced by low-intensity focused ultrasound (LIFU) in vitro. We found that the PFP@IR780@PTX@liposome NPs can specifically accumulate in prostate tumors after LIFU irradiation, as monitored by ultrasound and photoacoustic imaging. Meanwhile, docetaxel was controllably released from the nanoparticles to achieve enhanced chemotherapeutic therapy in vivo. These sonosensitive phase-changeable NPs can visually treat prostate cancers effectively and have a clinical potential.

Manual compass measurement and trigonometric determination of proptosis.

PURPOSE: To determine the accuracy of manual compass measurement and trigonometric determination of proptosis (MCMATDP). METHODS: This agreement study included 120 eyes without eye diseases or injury of 60 patients who visited the ophthalmic clinic of Peking University Shenzhen Hospital from February 2020 to June 2020. The absolute values of proptosis were measured by MCMATDP and computed tomography (CT). The differences between the two methods were shown by Bland-Altman plot. RESULTS: The cohort comprised 25 males and 35 females (average age 38.3 years). The absolute value of proptosis measured by CT was correlated with the MCMATDP. Further analysis showed that a 95% limit of agreement (LoA) was - 0.53 to 0.60 mm in the right eye and - 0.46 to 0.55 mm in the left eye between CT and MCMATDP. In addition, the 95% LoA was - 0.49 to 0.60 mm in both eyes between the two methods. All points were < 5% in Bland-Altman plots. CONCLUSIONS: Compared to CT, MCMATDP is rather consistent in proptosis measurement. The new method is feasible in clinical practice when measuring proptosis. With the development of non-contact intelligent measurement software and the continuous improvement in measurement accuracy, a non-invasive, simple, and inexpensive measurement mode is true based on the theory of MCMATDP.