DEMO-EM2: assembling protein complex structures from cryo-EM maps through intertwined chain and domain fitting.

The breakthrough in cryo-electron microscopy (cryo-EM) technology has led to an increasing number of density maps of biological macromolecules. However, constructing accurate protein complex atomic structures from cryo-EM maps remains a challenge. In this study, we extend our previously developed DEMO-EM to present DEMO-EM2, an automated method for constructing protein complex models from cryo-EM maps through an iterative assembly procedure intertwining chain- and domain-level matching and fitting for predicted chain models. The method was carefully evaluated on 27 cryo-electron tomography (cryo-ET) maps and 16 single-particle EM maps, where DEMO-EM2 models achieved an average TM-score of 0.92, outperforming those of state-of-the-art methods. The results demonstrate an efficient method that enables the rapid and reliable solution of challenging cryo-EM structure modeling problems.

A Highly Dispersed Cobalt Electrocatalyst with Electron-Deficient Centers Induced by Boron toward Enhanced Adsorption and Electrocatalysis for Room-Temperature Sodium-Sulfur Batteries.

As vitally prospective candidates for next-generation energy storage systems, room-temperature sodium-sulfur (RT-Na/S) batteries continue to face obstacles in practical implementation due to the severe shuttle effect of sodium polysulfides and sluggish S conversion kinetics. Herein, the study proposes a novel approach involving the design of a B, N co-doped carbon nanotube loaded with highly dispersed and electron-deficient cobalt (Co@BNC) as a highly conductive host for S, aiming to enhance adsorption and catalyze redox reactions. Crucially, the pivotal roles of the carbon substrate in prompting the electrocatalytic activity of Co are elucidated. The experiments and density functional theory (DFT) calculations both demonstrate that after B doping, stronger chemical adsorption toward polysulfides (NaPSs), lower polarization, faster S conversion kinetics, and more complete S transformation are achieved. Therefore, the as-assembled RT-Na/S batteries with S/Co@BNC deliver a high reversible capacity of 626 mAh g-1 over 100 cycles at 0.1 C and excellent durability (416 mAh g-1 over 600 cycles at 0.5 C). Even at 2 C, the capacity retention remains at 61.8%, exhibiting an outstanding rate performance. This work offers a systematic way to develop a novel Co electrocatalyst for RT-Na/S batteries, which can also be effectively applied to other transition metallic electrocatalysts.

Pectoral Nerve Blocks Under Direct Vision During Endoscopic-Assisted Transaxillary Breast Augmentation: A Novel, Effective Regional Blocking Approach.

BACKGROUND: Endoscopic-assisted transaxillary breast augmentation allows performing Pecs block under direct visualization. This study aimed to describe this new technique and demonstrat its short-term efficacy and safety with a preliminary clinical study. METHODS: Patients enrolled for transaxillary endoscopic-assisted prosthetic breast augmentation between February 2022 and March 2023 in two medical centers were included in the pectoral nerve block group. Postoperative VAS scores at 1, 4, 12, 24, 48, and 72 h, surgery duration, and the occurrence of nausea and vomiting were compared with a historical cohort of patients collected between February 2021 and January 2022 with the same inclusion criteria. RESULTS: 229 patients were included in the Pecs group and 116 patients were identified in the control group. No statistical difference was observed in patient characteristics. VAS score at postoperative 1 h and 72 h was similar between the two groups, whereas VAS score at postoperative 4 h, 12 h, 24 h and 48 h in Pecs group was significantly lower than control group. The occurrence of PONV in the Pecs group is significantly lower than in the control group. The duration of surgery is similar between the two groups. No block-related complication was observed in the Pecs group. CONCLUSION: A novel approach by combining pectoral nerve blocks with transaxillary endoscopic-assisted breast augmentation to perform blocks under direct vision was proposed and its short-term efficacy and safety was determined by this study. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Locating cellular contents during cryoFIB milling using cellular secondary-electron imaging.

Cryo-electron tomography (cryoET) is a powerful technology that allows in-situ observation of the molecular structure of tissues and cells. Cryo-focused ion beam (cryoFIB) milling plays an important role in the preparation of high-quality thin lamellar samples for cryoET studies, thus, promoting the rapid development of cryoET in recent years. However, locating the regions of interest in a large cell or tissue during cryoFIB milling remains a major challenge limiting cryoET applications on arbitrary biological samples. Here, we report an on-the-fly localization method based on cellular secondary electron imaging (CSEI), which is derived from a basic imaging function of the cryoFIB instruments and enables high-contrast imaging of the cellular contents of frozen-hydrated biological samples. Moreover, CSEI does not require fluorescent labels and additional devices. The present study discusses the imaging principles and settings for optimizing CSEI. Tests on several commercially available cryoFIB instruments demonstrated that CSEI was feasible on mainstream instruments to observe all types of cellular contents and reliable under different milling conditions. We established a simple milling-localization workflow and tested it using the basal body of Chlamydomonas reinhardtii.

P-doped porous carbon from camellia shell for high-performance room temperature sodium-sulfur batteries.

Room-temperature sodium-sulfur batteries are still hampered by severe shuttle effects and sluggish kinetics. Most of the sulfur hosts require high cost and complex synthesis process. Herein, a facile method is proposed to prepare a phosphorous doped porous carbon (CSBP) with abundant defect sites from camellia shell by oxidation pretreatment combined with H3PO4activation. The pretreatment can introduce pores and adjust the structure of biochar precursor, which facilitates the further activation of H3PO4and effectively avoids the occurrence of large agglomeration. Profiting from the synergistic effects of physical confinement and doping effect, the prepared CSBP/S cathode delivers a high reversible capacity of 804 mAh g-1after 100 cycles at 0.1 C and still maintains an outstanding capacity of 458 mAh g-1after 500 cycles at 0.5 C (1 C = 1675 mA g-1). This work provides new insights into the rational design of the microstructures of carbon hosts for high-performance room temperature sodium-sulfur batteries.

Analgesic Efficacy of Pectoral Nerve Blocks in Implant-Based Mammoplasty: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the analgesic effect of pectoral nerve block in implant-based mammoplasty. METHODS: EMbase, PubMed, Web of science, MEDLINE, CNKI, Wanfang Database, VIP and other databases were searched from establishment to February 2022 by computer to collect randomized controlled trials which applied pectoral nerve block in implant-based mammoplasty, and meta-analysis was conducted after data extraction and quality evaluation of the literature meeting the inclusion criteria. RESULTS: A total of 336 patients in seven RCT studies were included in this study. Pectoral nerve block has a significant effect on postoperative analgesia in patients with implant-based mammoplasty with 1h VAS score significantly reduced in the resting state (MD=-1.85, 95%CI: -2.64~-1.07, P<0.00001); VAS score was significantly decreased 4-6 hours after operation (MD=-1.51, 95%CI: -2.47~-0.55, P=0.002); postoperative opioid consumption was reduced (SMD=-1.37, 95%CI: -2.51~-0.24, P=0.02) in PECS block group; and the incidence of postoperative nausea and vomiting in the PECS block group was significantly lower (RR: 0.30, 95 %CI: 0.19-0.38, P<0.00001). CONCLUSIONS: The application of PECS block in submuscular implant-based mammoplasty can effectively reduce the degree of acute postoperative pain, opioid consumption and the incidence of postoperative nausea and vomiting, indicating its broad prospects in clinical application. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

What Can We Learn from Breast Implant Explantation: a 28-Year, Multicenter Retrospective Study of 1004 Explantation Cases.

BACKGROUND: Implant-based breast augmentation remains popular, but the controversy over the safety and longevity of implants has continued. An event-based analysis of reasons for implant explantation may provide us with some insight into the controversy. METHODS: Data from May 1994 to October 2022 of explantation cases from aesthetic breast augmentation in three medical centers were retrospectively reviewed. Patient characteristics, time to explantation, reasons for visit, the major reason for explantation and intraoperative findings were analyzed. RESULTS: A total of 522 patients with 1004 breasts were included in our study. Objective explantation reasons accounted for 34.0% in primary augmentation breasts and 47.6% in revision augmentation breasts, which were significantly different (p = 0.006). The most common complaint was dissatisfaction with breast appearance, followed by concerns about implant safety, poor hand feeling and pain. 43.5% of the implants worn for more than 10 years were removed for objective reasons, which was found significantly different with the proportion of objective reasons in implants removed within 1 year and 1-5 years postoperatively (p < 0.008). CONCLUSION: The proportion of different reasons for implant explantation varies across the times of surgeries and the years that the implant had been worn. As the years of implant wearing increase, the proportion of subjective reasons decreases in implant removal cases and objective reasons increase among them. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Association Between Body Weight and Removed Weight in Women Undergoing Reduction Mammaplasty-A 17-year Retrospective Study of 1777 Breasts.

BACKGROUND: Breast hypertrophy causes physical and psychological symptoms. Reduction mammaplasty is a surgical procedure to lessen discomfort. However, there is a dispute about whether the weight of breast resection is related to body weight. This study aims to provide Chinese data and assess the association between body weight and removed weight in women undergoing reduction mammaplasty. METHODS: Retrospective data were collected from 1777 breasts in a single center in 17 years. Simple linear regression analysis was performed to establish whether removed weight and removed weight ratio (removed weight/body weight) correlated with the body weight. The correlations were then analyzed again after grouping according to the removed weight. RESULTS: For all breasts included, removed weight or ratio positively correlates with body weight. When the removed weight is more than 1000g, there is no statistically significant correlation between body weight and removed breast weight. When removed per breast weight is more than 600g, there is no correlation between body weight and removed breast weight ratio. CONCLUSIONS: The correlation between body weight and removed weight or ratio decreased with increasing removed weight. When removed weight >600g, the degree of breast hypertrophy is not related to body shape. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Therapeutic study.

Childhood parental companionship, self-esteem and prosocial behavior in college students: A correlation analysis.

BACKGROUND: We aimed to evaluate the correlation of Childhood parental companionship, self-esteem and prosocial behavior in college students. METHODS: We conducted a survey to assess the childhood parental companionship, self-esteem and prosocial behavior in our college from November 1, 2021 to December 15, 2021. The parental companionship status questionnaire, Self-Esteem Scale (SES) and prosocial behavior questionnaire were used for survey. Pearson linear correlation analysis was used for evaluating the correlation of childhood parental companionship, self-esteem and prosocial behavior in college students. The Bootstrap method was used to test the potentially mediating effect. RESULTS: A total of 2186 college students were included. The average total companionship score was (60.52 ± 5.17), the average self-esteem scale score was (27.15 ± 8.56), the prosocial behavior questionnaire score was (61.19 ± 15.04). Pearson correlation analysis indicated that childhood parental companionship was positively correlated with self-esteem (r = 0.679) and prosocial behavior(r = 0.679) in included college students (all P < 0.05). Self-esteem had mediating effect on parental companionship and prosocial behavior of included college students, its mediating effect was -0.445, accounting for 77.92 % of the total effect. CONCLUSIONS: Childhood parental companionship is positively correlated with self-esteem and prosocial behavior, and self-esteem play a mediating role in the parental companionship and prosocial behavior of college students.

Knockdown of SGLT1 prevents the apoptosis of cardiomyocytes induced by glucose fluctuation via relieving oxidative stress and mitochondrial dysfunction.

Fluctuations in the concentration of glucose in the blood is more detrimental than a constantly high level of glucose with respect to the development of cardiovascular complications associated with diabetes mellitus (DM). Sodium glucose cotransporter 2 (SGLT2) inhibitors have been developed as antidiabetic drugs with cardiovascular benefits; however, whether inhibition of SGLT1 protects the diabetic heart remains to be determined. This study investigated the role of SGLT1 in rat H9c2 cardiomyocytes subjected to fluctuating levels of glucose and the underlying mechanisms. The results indicated that knockdown of SGLT1 restored cell proliferation and suppressed the cytotoxicity associated with fluctuating glucose levels. Oxidative stress was induced in H9c2 cells subjected to fluctuating glucose levels, but these changes were effectively reversed by knockdown of SGLT1, as manifested by reductions in the level of intracellular reactive oxygen species and increased antioxidant activity. Further study demonstrated that knockdown of SGLT1 attenuated the mitochondrial dysfunction in H9c2 cells exposed to fluctuating glucose levels, by restoring mitochondrial membrane potential and promoting mitochondrial fusion. In addition, knockdown of SGLT1 downregulated the expression of Bax, upregulated the expression of Bcl-2, and reduced the activation of caspase-3 in H9c2 cells subjected to fluctuating levels of glucose. Collectively, our results show that knockdown of SGLT1 ameliorates the apoptosis of cardiomyocyte caused by fluctuating glucose levels via regulating oxidative stress and combatting mitochondrial dysfunction.

Design and characteristics of tunable in-plane optofluidic lens actuated by viscous force.

In this Letter, we report a tunable in-plane optofluidic lens based on a new regulation method. The viscous force (VF) adjusts a 68# white mineral oil-air interface and focal length (f). Two glass plates bonded by ultraviolet adhesive strips form a lens chamber. Liquid enters the chamber by capillary action and forms a convex interface due to VF. As the liquid filling amount increases, VF is enhanced, and the interface deforms. Because of the uneven VF, interface is aspheric, which can reduce the lens aberration. Bendings on both sides of the interface caused by edge effect lead to an even polynomial profile of the entire interface, and they can be used for aberration correction of an in-plane spherical reflector. Experiments demonstrate the continuous tuning of f from 17.7 to 45.1 mm. The positive longitudinal spherical aberration (LSA) is effectively suppressed below 0.078 when f<35.5mm. Interface with a large negative LSA is used for spherical reflector aberration correction. Simulation results proved that the light spot improvement rate is>90%, and the maximum reached 99%.

Glucose fluctuation accelerates cardiac injury of diabetic mice via sodium-dependent glucose cotransporter 1 (SGLT1).

Recent studies have shown that blood glucose fluctuation is associated with complications of diabetes mellitus (DM). SGLT1 (sodium-dependent glucose cotransporter 1), is highly expressed in pathological conditions of heart, and is expressed in cardiomyocytes induced by high glucose. Herein, we constructed a diabetic mouse model with glucose fluctuation to investigate whether SGLT1 is involved in glucose fluctuation-induced cardiac injury. Echocardiography, histology examination, and TUNEL staining were performed to evaluate cardiac dysfunction and damage. To assess glucose fluctuation-induced oxidative stress, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. To assess mitochondrial dysfunction, mitochondrial membrane potential (MMP), ATP content, mitochondrial respiratory chain complex activity, and expression of mitochondrial fusion and fission proteins were determined. The results indicated that diabetic mice with glucose fluctuation showed elevation of cardiac SGLT1 expression, left ventricular dysfunction, oxidative stress and mitochondrial dysfunction. Knockdown of SGLT1 could abrogate the effects of glucose fluctuation on cardiac injury. Thus, our study highlighted that SGLT1 plays an important role in glucose fluctuation induced cardiac injury through oxidative stress and mitochondrial dysfunction.

Intermittent high glucose induces pyroptosis of rat H9C2 cardiomyocytes via sodium-glucose cotransporter 1.

Cardiomyocyte death is an important pathogenic process in cardiac complications of diabetes. Diabetic patients often suffer glycemic variability. Pyroptosis is a form of programmed cell death triggered by inflammasomes and related with caspase-1 and gasdermin D activation. The present study was designed to examine the effects of intermittent high glucose simulating glycemic variability on the pyroptosis of cardiomyocytes in vitro. Rat H9C2 cardiomyocytes were incubated with normal glucose (NG), constant high glucose (CHG) and intermittent high glucose (IHG). Results showed that compared to CHG treatment, IHG further inhibited cell proliferation and promoted cell death of H9C2 cardiomyocytes. In addition, IHG upregulated higher levels of the expressions of inflammasome NLR family pyrin domain containing 3 (NLRP3) and adaptor protein apoptosis-associated speck-like protein containing CARD domain (ASC) and increased higher levels of activated caspase-1 and gasdermin D than CHG treatment. Moreover, the production of reactive oxygen species (ROS) and activation of NF-κB that is induced by IHG were significantly higher than that induced by CHG. Knockdown of sodium-glucose cotransporters 1 (SGLT1) in H9C2 cardiomyocytes was performed and the effects of SGLT1 on IHG-induced pyroptosis was evaluated. The results demonstrated that knockdown of SGLT1 partially reduced IHG-induced pyroptosis, ROS generation and NF-κB activation. Our results indicated that IHG is harmful to cardiomyocytes and it might be partially because of the SGLT1-depedent pyroptosis in cardiomyocytes.

Construction of bridged polycycles through dearomatization strategies.

Bridged polycycles are privileged molecular skeletons with wide occurrence in bioactive natural products and pharmaceuticals. Therefore, they have been the pursing target molecules of numerous chemists. The rapid and convenient generation of sp3-rich complex three-dimensional molecular skeletons from simple and easily available aromatics has made dearomatization a highly valuable synthetic tool for the construction of rigid and challenging bridged rings. This review summarizes the-state-of-the-art advances of dearomatization strategies in the application of bridged ring formation, discusses their advantages and limitations and the in-depth mechanism, and highlights their synthetic value in the total synthesis of natural products. We wish this review will provide an important reference for medicinal and synthetic chemists and will inspire further development in this intriguing research area.

Curved terahertz surface plasmonic waveguide devices.

Strongly confined surface waves can be achieved on periodically structured metal surfaces and are known as spoof surface plasmon polaritons (SPPs). In this work, several terahertz SPP devices based on curved waveguides are demonstrated. The transmittance and bending loss of 90-degree curved spoof SPP waveguides with a radius of curvature ranging from 200 to 2300 µm are investigated to identify the regime for high transmission. A commutator is designed and experimentally demonstrated. Furthermore, coupling equations are derived and verified for efficient coupling between bend-straight waveguides and between bend-bend waveguides. The results will be of great value for future integrated terahertz plasmonic systems.

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma.

BACKGROUND Protein kinase membrane-associated tyrosine/threonine (PKMYT1) has been found in many tumors, but its association with clear cell renal cell carcinoma (ccRCC) remains unclear. MATERIAL AND METHODS PKMYT1 expression in ccRCC was examined in the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource databases. The correlation between PKMYT1 expression and clinicopathological parameters was explored via the chi-square test. Receiver operating characteristic curves were used to estimate the diagnostic performance of PKMYT1. Kaplan-Meier curves, a Cox model, nomogram, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA) were used to evaluate the prognostic value and clinical utility of PKMYT1. Genes coexpressed with PKMYT1 in ccRCC were identified based on TCGA, the gene expression profiling interactive, and cBioPortal. Gene Set Enrichment Analysis revealed biological pathways associated with PKMYT1 in ccRCC. RESULTS Weighted gene coexpression network analysis identified PKMYT1 as one of the genes most significantly correlated with progression of histological grade. PKMYT1 was significantly upregulated in ccRCC compared with normal tissue (P<0.001), with a trend toward differentiating between individuals with ccRCC and those who were healthy (area under the curve=0.942). High PKMYT1 expression was correlated with unsatisfactory survival (hazard ratio=1.67, P=0.001), indicating that it is a risk factor for ccRCC. A nomogram incorporating PKMYT1 level was created and showed a clinical net benefit. PKMYT1 was strongly positively correlated with the anti-silencing function of 1B histone chaperone (ASF1B) gene in ccRCC. CONCLUSIONS PKMYT1 is upregulated in ccRCC and its presence indicates poor prognosis, making it a potential therapeutic target for ccRCC.

Development and Identification of a Nomogram Prognostic Model for Patients with Primary Clear Cell Carcinoma of the Liver.

BACKGROUND Primary clear cell carcinoma of the liver (PCCCL) is an infrequent variant of primary hepatocellular carcinoma (HCC), we retrospectively performed a large population-based cohort study to elucidate the relationships between demographic, carcinoma- and therapy-specific variables and overall survival (OS). MATERIAL AND METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried to extract data on 419 patients with pathologically confirmed PCCCL from 1988 to 2015. A nomogram with good accuracy was formulated to predict long-term survival of PCCCL patients. RESULTS The OS for PCCCL patients was 25.6 months (95% confidence interval [CI]: 22.2-29 months), the overall 1-year, 3-year, and 5-year survival rates were 59.5%, 39.3%, and 29.9%, respectively. Log-rank analysis revealed that there was no statistically significant discrepancy in clinical outcome between PCCCL and common-type HCC after propensity-matched analysis. Multivariate Cox analysis confirmed that larger lesions (>96 mm), distant metastases and elevated alpha-fetoprotein (AFP) levels were independent prognostic factors for undesirable outcome. Conversely, surgery was an independent protective factor (hazard ratio [HR]=0.23, 95% CI 0.17-0.31), which significantly boosted OS by virtually 35 months (47.3 months versus 12.7 months, P<0.001). Radiotherapy or chemotherapy was not associated with OS for PCCCL patients (both P>0.05). The nomogram incorporated 4 independent prognostic factors and its concordance index for predicting survival was 0.761. CONCLUSIONS The prognosis of PCCCL resembled that of common-type HCC. Larger lesions, distant metastases, and enhanced AFP levels were associated with unsatisfactory prognosis. Surgery fulfill favorable prognosis while radiotherapy or chemotherapy exerted no significant effects on survival.

The signaling axis of Rac1-TFEB regulates autophagy and tumorigenesis.

Macroautophagy (hereafter referred to as autophagy) plays essential roles in cellular and organismal homeostasis. Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis. It is not fully understood how the function of TFEB in autophagy pathway is regulated. Here, we show that Rac1 GTPase is a negative modulator of autophagy by targeting TFEB. Mechanistically, Rac1 reduces autophagy flux by repressing the expressing of autophagy genes. Further investigation revealed that under nutrient-rich conditions, mammalian target of rapamycin (mTOR) phosphorylates TFEB to facilitate the interaction between Rac1 and TFEB. Biochemical dissection uncovered that guanosine 5'-triphosphate (GTP)-bound form of Rac1 selectively interacts with phosphorylated TFEB. This inhibitory interaction prevents the dephosphorylation and nucleus translocation of TFEB, which hampers the transcriptional activation of autophagy-related genes. Furthermore, Rac1-TFEB axis appeared to be important for tumorigenesis, as overexpression of dephosphorylated mutant of TFEB was able to delay the tumor growth driven by Rac1 overexpression. Together, this study not only elucidates a previously uncharacterized autophagy regulation mechanism involving Rac1 and TFEB under physiological and pathological conditions but also suggests a strategy to treat cancers that are driven by Rac1 overexpression.