ARID1A regulates DNA repair through chromatin organization and its deficiency triggers DNA damage-mediated anti-tumor immune response.

AT-rich interaction domain protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. Loss of ARID1A leads to DNA repair defects. Here, we show that ARID1A plays epigenetic roles to promote both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates chromatin loops formation by recruiting RAD21 and CTCF to DSBs. Simultaneously, ARID1A facilitates transcription silencing at DSBs in transcriptionally active chromatin by recruiting HDAC1 and RSF1 to control the distribution of activating histone marks, chromatin accessibility, and eviction of RNAPII. ARID1A depletion resulted in enhanced accumulation of micronuclei, activation of cGAS-STING pathway, and an increased expression of immunomodulatory cytokines upon ionizing radiation. Furthermore, low ARID1A expression in cancer patients receiving radiotherapy was associated with higher infiltration of several immune cells. The high mutation rate of ARID1A in various cancer types highlights its clinical relevance as a promising biomarker that correlates with the level of immune regulatory cytokines and estimates the levels of tumor-infiltrating immune cells, which can predict the response to the combination of radio- and immunotherapy.

Risk factors and clinical impact of seroma formation following laparoscopic inguinal hernia repair: a retrospective study.

BACKGROUND: Although laparoscopic inguinal hernia repair (LIHR) has advantages over open surgery, postoperative seroma formation remains an issue. This study aimed to investigate the risk factors and clinical outcomes of seroma formation in patients undergoing LIHR. METHODS: From January 2016 to March 2023, clinical data of patients who underwent LIHR were retrospectively analyzed. Patients who developed seroma and those who did not were classified into the seroma and non-seroma groups, respectively. The demographic and clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed for variables of interest. The receiver operating characteristic curve was used to evaluate the risk factors of the binary logistic model, and the cutoff value for each risk factor was obtained. RESULTS: Data of 128 patients were evaluated. Compared with patients in the non-seroma group, those in the seroma group had a higher body mass index (BMI) (P < 0.001), more direct hernias (P < 0.001), larger hernial orifice size (P < 0.001), more laparoscopic total extraperitoneal hernioplasty (TEP) (P < 0.001), more frequent reduction of hernial sac (P = 0.011), and lower preoperative serum albumin level (PSAL) (P < 0.001). Multivariate logistic regression analyses performed on these variables showed that high BMI (P = 0.005), large hernial orifice (P = 0.001), TEP (P = 0.033), and low PSAL (P = 0.009) were risk factors for seroma formation. Compared with the non-seroma group, the seroma group exhibited a higher numerical rating scale score for postoperative pain (P < 0.001), and longer hospital stays (P = 0.032). CONCLUSIONS: BMI (> 24.5 kg/m2), hernial orifice size (> 2.5 cm), TEP, and PSAL (< 32.5 g/L) were independent risk factors of postoperative seroma formation in patients who underwent LIHR. Although most seromas resolve spontaneously without surgical intervention, seroma formation results in increased patient pain and prolonged hospital stay.

ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition.

The inhibitor of DNA-binding 3 (ID3) is a transcriptional regulator that limits interaction of basic helix-loop-helix transcription factors with their target DNA sequences. We previously reported that ID3 loss is associated with mutational signatures linked to DNA repair defects. Here we demonstrate that ID3 exhibits a dual role to promote DNA double-strand break (DSB) repair, particularly homologous recombination (HR). ID3 interacts with the MRN complex and RECQL helicase to activate DSB repair and it facilitates RAD51 loading and downstream steps of HR. In addition, ID3 promotes the expression of HR genes in response to ionizing radiation by regulating both chromatin accessibility and activity of the transcription factor E2F1. Consistently, analyses of TCGA cancer patient data demonstrate that low ID3 expression is associated with impaired HR. The loss of ID3 leads to sensitivity of tumor cells to PARP inhibition, offering new therapeutic opportunities in ID3-deficient tumors.

Selective inhibitors of bromodomain BD1 and BD2 of BET proteins modulate radiation-induced profibrotic fibroblast responses.

Radiotherapy can induce various adverse effects including fibrosis in cancer patients. Radiation-induced aberrant expression of profibrotic genes has been associated with dysregulated epigenetic mechanisms. Pan-BET (bromodomain and extraterminal domain) inhibitors, such as JQ1 and I-BET151, have been reported to attenuate the profibrotic response after irradiation. Despite their profound preclinical efficacy, the clinical utility of pan-inhibitors is limited due to observed cytotoxicicities. Recently, inhibitors were developed that selectively target the first (BD1) and second (BD2) bromodomain of the BET proteins (iBET-BD1 [GSK778] and iBET-BD2 [GSK046]). Here, their potential to attenuate radiation-induced fibroblast activation with low-toxicity was investigated. Our results indicated that cell proliferation and cell cycle progression in fibroblasts from BJ cells and six donors were reduced when treated with I-BET151 and iBET-BD1, but not with iBET-BD2. After irradiation, induction of DGKA and profibrotic markers, especially COL1A1 and ACTA2, was attenuated with all BET inhibitors. H3K27ac enrichment was similar at the DGKA enhancer region after I-BET151 treatment and irradiation, but was reduced at the COL1A1 transcription start site and the ACTA2 enhancer site. iBET-BD2 did not change H3K27ac levels in these regions. BRD4 occupancy at these regions was not altered by any of the compounds. Cell migration activity was measured as a characteristic independent of extracellular matrix production and was unchanged in fibroblasts after irradiation and BET inhibitor-treatment. In conclusion, iBET-BD2 efficiently suppressed radiation-induced expression of DGKA and profibrotic markers without showing cytotoxicity. Thus BD2-selective targeting is a promising new therapeutic avenue for further investigations to prevent or attenuate radiotherapy-induced fibrosis.

A Retrospective Study of the Safety and Efficacy of Endoscopic Radiofrequency Therapy Under Direct Vision in 59 Patients with Gastroesophageal Reflux Disease from 2 Centers in Beijing, China Using the Gastroesophageal Reflux Disease Questionnaire.

BACKGROUND This retrospective study from 2 centers in Beijing, China aimed to assess the safety and efficacy of endoscopic radiofrequency therapy under direct vision in 59 patients with gastroesophageal reflux disease (GERD) using the gastroesophageal reflux disease questionnaire (GerdQ). MATERIAL AND METHODS Fifty-nine GERD patients who underwent endoscopic radiofrequency treatment were included. Patients were divided into 2 groups: the endoscopic radiofrequency therapy under direct vision group and the non-direct vision radiofrequency therapy group. Indicators such as GerdQ score, lower esophageal sphincter (LES) pressure, DeMeester score, acid exposure time, and proton pump inhibitors (PPIs) use were collected before and after radiofrequency treatment. Postoperative complications were also recorded. The efficacy and safety of endoscopic radiofrequency therapy under direct vision were evaluated by comparing the indicators of patients in the 2 groups. RESULTS At 3 months after radiofrequency treatment, patients in the endoscopic radiofrequency therapy under direct vision group improved significantly in GerdQ score, decreased from 11.0 (10.0, 12.0) to 6.0 (6.0, 8.0), better than patients in the non-direct vision radiofrequency therapy group, and the better improvements remained at 12 months after the procedure (P<0.05). At 6 months after treatment, patients in the endoscopic radiofrequency therapy under direct vision group had significant improvements in LES pressure, which increased from 8.15 (3.18, 12.88) mmHg to 15.20 (10.25, 27.03) mmHg (P<0.05). There were no severe complications in our trial. CONCLUSIONS When compared with non-visualized endoscopic radiofrequency therapy, treatment under direct vision was safer and improved the GerdQ score and LES pressure at up to 12 months.

Peroral endoscopic myotomy for the treatment of achalasia after failed pneumatic dilation.

BACKGROUND AND AIMS: POEM is a rescue endoscopic therapy for patients who had previously failed surgical or endoscopic treatment. However, data regarding its effectiveness after failed pneumatic dilation (PD) and its long-term effects are limited. We aimed to retrospectively investigate the long-term outcomes in patients who had undergone POEM after failed PD. METHODS: Data from 66 achalasia patients with a 2-year follow-up period were analyzed. Intraprocedural events were compared between the first POEM group (patients without prior-endoscopic intervention) and prior PD group (patients who had pre-POEM PD). Symptom evaluation, HRM and 24 h-pH DeMeester scores between the two groups were performed at 2 years after the POEM procedure. Muscularis externa samples were obtained from the lower esophagus using POEM to assess the muscle fibrosis with Azan-Mallory staining. RESULTS: POEM was successfully performed for all achalasia patients. During the 2-year follow-up period, the success rate of POEM was 96.15% (25/26) for patients with prior PD and 95% (38/40) with primary POEM. For patients with type II achalasia and who underwent prior PD, the post-procedure DeMeester score was higher compared to patients who underwent POEM only (P < 0.05). A larger number of patients who underwent primary POEM (27.50%, 11/40) complained of mild heartburn compared to patients who underwent POEM after PD (7.69%, 2/26) (P < 0.05). With regards to fibrosis, the majority of patients who underwent POEM only were classified as F-1 (45.00%, 18/40), while the majority of patients who underwent prior PD were classified as F-2 (42.3%, 11/26). The degree of fibrosis was significantly different between the two groups (P < 0.05). Both surgical time and prior PD were correlated with the degree of fibrosis (P < 0.05). CONCLUSIONS: Despite the technical challenges, pre-POEM endoscopic treatment does not impact the safety and efficacy of POEM in achalasia patients. Longer follow-up studies using larger cohorts are needed to determine long-term outcomes and complications of POEM.

Characterization of an Ecdysteroid-Regulated 16 kDa Protein Gene in Chinese Oak Silkworm, Antheraea pernyi (Lepidoptera: Saturniidae).

A large number of ecdysteroid-regulated 16 kDa proteins (ESR16s) of insects have been isolated and annotated in GenBank; however, knowledge on insect ESR16s remain limited. In the present study, we characterized an ecdysteroid-regulated 16 kDa protein gene isolated in Chinese oak silkworm, Antheraea pernyi Guérin-Méneville ('ApESR16' in the following), an important silk-producing and edible insect. The obtained cDNA sequence of ApESR16 is 1,049 bp, harboring an open reading frame of 441 bp that encodes a polypeptide of 146 amino acids. CD-search revealed that ApESR16 contains the putative cholesterol/lipid binding sites on conserved domain Npc2_like (Niemann-Pick type C-2) belonging to the MD-2-related lipid-recognition superfamily. Sequence comparison revealed that ApESR16 exhibits 51-57% identity to ESR16s of lepidopteran insects, 36-41% identity to ESR16 or NPC2a of nonlepidopteran insects, and 28-32% identity to NPC2a of vertebrates, indicating a high sequence divergence during the evolution of animals. Phylogenetic analysis found that the used sequences were divided into two groups corresponding to vertebrates and invertebrates, and the used insect sequences were also well clustered according to their families. The A. pernyi ESR16 mRNA is expressed during all four developmental stages and in all tested tissues. Injection of 20-hydroxyecdysone (20-E) into A. pernyi diapausing pupae triggering diapause termination induced upregulation of ESR16 mRNA compared to the diapausing pupae, with the highest expression level at day 2 in the ovaries but day 12 in the fat body. Our results suggested that ApESR16 might be a diapause-related gene and plays a vital role in the pupal diapause of A. pernyi.

Corrosion Resistance of ZnO Nanorod Superhydrophobic Coatings with Rose Petal Effect or Lotus Leaf Effect.

Superhydrophobic ZnO nanorods coatings with a strong adhesive force to the surface (rose petal effect) or a low sliding angle (lotus leaf effect) were fabricated on the zinc plate by the hydrothermal plus sol-gel method. The corrosion resistance and durability of the superhydrophobic coatings in 5 wt% NaCl solution were investigated. The coating with loose ZnO nanostructure on ZnO nanorods shows a high adhesive force to water with low corrosion resistance, while the coating with a layer of dense nanotubes on nanorods exhibits a low adhesive to water with a high corrosion resistance due to a layer of trapped air among micro/nanostructures, which can delay the penetration of corrosive media. It can be found that the nanorods coating with lotus leaf effect lost its superhydrophobicity after 5150 s immersion in salt solution and the water repellency model is transformed from Cassie state to Wenzel state.

Joint Hartley-domain and time-domain equalizer for a 200-G (4×56-Gbit/s) optical PAM-4 system using 10G-class optics.

In this paper, we experimentally demonstrate a 200-G (4×56-Gbit/s) optical 4-level pulse-amplitude modulation (PAM-4) system using 10G-class optics over 10-km standard single-mode fiber and propose a joint Hartley-domain equalizer (HDE) and time-domain equalizer (TDE) algorithm for efficiently compensating the serious high-frequency distortions caused by the bandwidth-limited devices. To the best of our knowledge, the first HDE based on Hartley transform is designed for an optical PAM-4 system. Owing to the real-valued and self-inverse properties of the Hartley transform, the HDE has advantages in processing the real-valued PAM-4 signal. The experimental results show that the joint HDE and TDE algorithm has a better performance than only the HDE or only the TDE. Meanwhile, for obtaining a desired bit error rate, the computational complexity of the joint HDE and TDE algorithm is approximately 6% that of only the TDE with larger tap number. In conclusion, the joint HDE and TDE algorithm shows great potential for high-speed and cost-sensitive optical PAM-4 systems.

Effect of Dexmedetomidine combined with sufentanil for post- thoracotomy intravenous analgesia:a randomized, controlled clinical study.

BACKGROUND: Few studies have investigated the use of dexmedetomidine in patient-controlled intravenous analgesia (PCIA) after thoracic surgery. This study to evaluate the effect of dexmedetomidine combined with sufentanil for PCIA after thoracotomy under general anaesthesia. METHODS: Ninety-seven adults patients scheduled for thoracotomy surgery. All two groups received PCIA with either sufentanil alone (control group) or combining dexmedetomidine with sufentanil (dexmedetomidine group). Hemodynamic measurements, visual analog scale (VAS) scores at rest and at coughing, Ramsay sedation score (RSS), analgesic consumption, and postoperative nausea and vomiting (PONV) as well as drug-related adverse effects were compared at 2, 6, 12, 24, 36 and 48 h postoperatively. RESULTS: In the patients of the dexmedetomidine group, compared to the control group, the pain scores at rest or at coughing during 48 h postoperatively were lower (P < 0.001), the sedation scores were lower, the consumption of sufentanil and rescue meperidine were lower, and the number of episode of moderate PONV was three times lower. No signs of toxicity or local complications were observed. There was a non-significant trend for a lower HR and BP in the dexmedetomidine group vs. CONCLUSION: The combining dexmedetomidine with sufentanil for post-thoracotomy PCIA can improve pain control together with the decrease in sufentanil requirements, and improve postoperative patient's satisfaction compared with sufentanil alone in PCIA. TRIAL REGISTRATION: This trial was retrospectively registered on 27 April 2016 at the Chinese Clinical Trial Register (number: ChiCTR-ONC-16008376 ).

Crystal structure and functional implications of the tandem-type universal stress protein UspE from Escherichia coli.

BACKGROUND: The universal stress proteins (USP) family member UspE is a tandem-type USP that consists of two Usp domains. The UspE expression levels of the Escherichia coli (E. coli) become elevated in response to oxidative stress and DNA damaging agents, including exposure to mitomycin C, cadmium, and hydrogen peroxide. It has been shown that UspA family members are survival factors during cellular growth arrest. The structures and functions of the UspA family members control the growth of E. coli in animal hosts. While several UspA family members have known structures, the structure of E. coli UspE remains to be elucidated. RESULTS: To understand the biochemical function of UspE, we have determined the crystal structure of E. coli UspE at 3.2 Å resolution. The asymmetric unit contains two protomers related by a non-crystallographic symmetry, and each protomer contains two tandem Usp domains. The crystal structure shows that UspE is folded into a fan-shaped structure similar to that of the tandem-type Usp protein PMI1202 from Proteus mirabilis, and it has a hydrophobic cavity that binds its ligand. Structural analysis revealed that E. coli UspE has two metal ion binding sites, and isothermal titration calorimetry suggested the presence of two Cd(2+) binding sites with a Kd value of 38.3-242.7 µM. Structural analysis suggested that E. coli UspE has two Cd(2+) binding sites (Site I: His117, His 119; Site II: His193, His244). CONCLUSION: The results show that the UspE structure has a hydrophobic pocket. This pocket is strongly bound to an unidentified ligand. Combined with a previous study, the ligand is probably related to an intermediate in lipid A biosynthesis. Subsequently, sequence analysis found that UspE has an ATP binding motif (Gly(269)- X2-Gly(272)-X9-Gly(282)-Asn) in its C-terminal domain, which was confirmed by in vitro ATPase activity monitored using Kinase-Glo® Luminescent Kinase Assay. However, the residues constituting this motif were disordered in the crystal structure, reflecting their intrinsic flexibility. ITC experiments revealed that the UspE probably has two Cd(2+) binding sites. The His117, His 119, His193, and His244 residues within the ß-barrel domain are necessary for Cd(2+) binding to UspE protein. As mentioned above, USPs are associated with several functions, such as cadmium binding, ATPase function, and involvement in lipid A biosynthesis by some unknown way.

Bubble CPAP Support after Discontinuation of Mechanical Ventilation Protects Rat Lungs with Ventilator-Induced Lung Injury.

BACKGROUND: Bubble continuous positive airway pressure (BCPAP) has been used in neonates with respiratory distress for decades, but its lung-protective effect and underlying mechanism has not been investigated. OBJECTIVES: To test the hypothesis that BCPAP use after extubation decreases lung injury and that alterations to lung nitric oxide synthase (NOS) 3 expression may be one of the underlying mechanisms. METHODS: We compared gas exchange, lung injury severity, and lung NOS expression among rats with ventilator-induced lung injury (VILI) treated with either BCPAP or spontaneous breathing. After high tidal volume ventilation for 30 min, the rats were randomly divided to three groups: a control group underwent spontaneous breathing (n = 7), and two BCPAP groups were treated with the bubble technique with either a 2.5-mm-diameter (n = 7) or a 5.5-mm-diameter (n = 7) expiratory limb for 2 h. RESULTS: The bubble technique (2.5 and 5.5 mm diameter combined) resulted in a significantly higher PaO2, decreased alveolar protein levels (1.01 vs. 1.43 mg/kg, p < 0.05), a lower lung injury score (3.87 vs. 4.86, p < 0.05), and decreased NOS3 expression (1.99 vs. 3.32, p < 0.05) compared to spontaneous breathing in the control group. BCPAP with a 2.5-mm-diameter and with a 5.5-mm-diameter expiratory limb was not different with regard to gas exchange, alveolar protein levels, and lung injury scores, but there was a trend for lower NOS3 expression in the 5.5-mm group (1.41 vs. 2.56, p = 0.052). CONCLUSIONS: BCPAP decreases lung injury in rats with VILI after stopping mechanical ventilation. Attenuation of lung NOS3 expression may be one of the underlying mechanisms.

Inhibition of biofilm in Bacillus amyloliquefaciens Q-426 by diketopiperazines.

Biofilm formation can make significant effects on bacteria habits and biological functions. In this study, diketopiperazines (DKPs) produced by strain of Bacillus amyloliquefaciens Q-426 was found to inhibit biofilm formed in the gas-liquid interface. Four kinds of DKPs were extracted from B. amyloliquefaciens Q-426, and we found that 0.04 mg ml(-1) DKPs could obviously inhibit the biofilm formation of the strain. DKPs produced by B. amyloliquefaciens Q-426 made a reduction on extracellular polymeric substance (EPS) components, polysaccharides, proteins, DNAs, etc. Real-time PCR was performed to determine that whether DKPs could make an obvious effect on the expression level for genes related to biofilm formation in the strain. The relative expression level of genes tasA, epsH, epsG and remB which related to proteins, extracellular matrix, and polysaccharides, were downregulated with 0.04 mg ml(-1) DKPs, while the expression level of nuclease gene nuc was significantly upregulated. The quantitative results of the mRNA expression level for these genes concerted with the quantitative results on EPS levels. All of the experimental results ultimately indicated that DKPs could inhibit the biofilm formation of the strain B. amyloliquefaciens Q-426.

Remote intrathecal morphine preconditioning confers cardioprotection via spinal cord nitric oxide/cyclic guanosine monophosphate/protein kinase G pathway.

BACKGROUND: Remote intrathecal morphine preconditioning (RMPC) induces cardioprotection, but the underlying mechanisms of this effect is unknown. The aim of this study was to investigate the role of spinal cord nitric oxide/cyclic guanosine monophosphate/protein kinase G (NO/cGMP/PKG) signal pathway in the cardioprotection of RMPC in rats. MATERIALS AND METHODS: Anesthetized, open chest, male Sprague-Dawley rats were assigned to one of eight treatment groups 3 d after intrathecal catheter placement. Before ischemia and reperfusion, RMPC received intrathecal morphine (3 µg/kg) by three cycles of 5-min infusions interspersed with 5-min infusion free periods. Intrathecally administrated a nonspecific nitric oxide synthase (NOS) inhibitor Nω-Nitro-L-arginine methyl ester (30 nmol), a specific guanylate cyclase inhibitor oxadiazolo [4,3-a] quinoxalin-1-one (11 nmol) and PKG inhibitor KT-5823 (20 pmol) 10 min before RMPC was used to evaluate the role of NO/cGMP/PKG of spinal cord. Ischemia and reperfusion injury were then induced by 30 min of left coronary artery occlusion, followed by 120 min of reperfusion. Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. The content of cyclic guanosine monophosphate in the thoracic spinal cord was determined by radioimmunity protocol; the contents of nitric oxide and activity of NOS in the thoracic spinal cord were determined by nitrate reductase reduction and colorimetric methods; the expression of neuronal NOS (nNOS) and PKG in the thoracic spinal cord were determined by immunohistochemical and Western blotting method; the expression of nNOS messenger RNA was determined by reverse transcription-polymerase chain reaction method. RESULTS: RMPC group markedly reduced the infarct size compared with the control group. However, the cardioprotection of RMPC could be abolished by pretreatment with Nω-Nitro-L-arginine methyl ester, Oxadiazolo [4,3-a] quinoxalin-1-one, and KT-5823. RMPC enhanced nitric oxide , NOS, and cyclic guanosine monophosphate levels in the spinal cord. Meanwhile, RMPC increased PKG and nNOS protein or messenger RNA expression in the spinal cord. CONCLUSIONS: Spinal cord NO/cGMP/PKG signaling pathway mediates RMPC-induced cardioprotective effect.

[The interactions between natural products and OATP1B1].

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.

Cellular responses associated with ROS production and cell fate decision in early stress response to iron limitation in the diatom Thalassiosira pseudonana.

Investigation of how diatoms cope with the rapid fluctuations in iron bioavailability in marine environments may facilitate a better understanding of the mechanisms underlying their ecological success, in particular their ability to proliferate rapidly during favorable conditions. In this study, using in vivo biochemical markers and whole-cell iTRAQ-based proteomics analysis, we explored the cellular responses associated with reactive oxygen species (ROS) production and cell fate decision during the early response to Fe limitation in the centric diatom Thalassiosira pseudonana. Fe limitation caused a significant decrease in Photosystem (PS) II photosynthetic efficiency, damage to the photosynthetic electron transport chain in PS I, and blockage of the respiratory chain in complexes III and IV, which could all result in excess ROS accumulation. The increase in ROS likely triggered programmed cell death (PCD) in some of the Fe-limited cells through synthesis of a series of proteins involved in the delicate balance between pro-survival and pro-PCD factors. The results provide molecular-level insights into the major strategies that may be employed by T. pseudonana in response to Fe-limitation: the reduction of cell population density through PCD to reduce competition for available Fe, the reallocation of intracellular nitrogen and Fe to ensure survival, and an increase in expression of antioxidant and anti-PCD proteins to cope with stress.

Influence of seismic loading on segment opening of a shield tunnel.

The influence of seismic loading on segment opening of a shield tunnel was explored using the dynamic finite element method to analyze the distribution of segment opening under multidirectional seismic loading, combined with a typical engineering installation. The calculation of segment opening was deduced from equivalent continuous theory and segment opening was obtained through calculations. The results show that the scope of influence of the foundation excavation on segment opening is mainly resigned to within 5 segment rings next to the diaphragm wall and 4 joints nearest the working well when the tunnel is first excavated followed by the working well in the excavation order. The effect of seismic loading on segment opening is significant, and the minimum increase of the maximal segment opening owing to seismic loading is 16%, while that of the average opening is 27%. Segment opening under bidirectional coupled seismic loading is significantly greater than that under one-dimensional seismic loading. On the basis of the numerical calculations, the seismic acceleration and segment opening caused by seismic action were normalized, and a new calculation method was proposed for predicting the maximal segment opening of a shield tunnel at different depths under conditions of seismic loading.

Rough Ag2S@H-CeO2 photonic nanocomposites for effective eradication of drug-resistant bacteria and improved healing of infected cutaneous wounds.

With the continuous increasing threat of drug-resistant bacteria induced cutaneous wound infections, there is a growing demand for novel effective antibiotics-alternative antibacterial strategies for clinical anti-infective therapy. Here, we report the fabrication and antibacterial efficacy of Ag2S@H-CeO2 photonic nanocomposites with rough surface through in-situ growth of Ag2S nanoparticles on CeO2 hollow spheres. With excellent photothermal property and peroxidase-like activity, as well as increased bacterial adhesion, the photonic nanocomposites demonstrated a broad-spectrum synergistic antibacterial effect against Gram-positive, Gram-positive bacteria and fungi as well biofilm in vitro. Significantly, the nanocomposites can effectively eradicate drug-resistant bacteria such as Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL E. coli). Notably, in vivo assessments validated its synergistic therapeutic potential in the treatment of MRSA-infected cutaneous wounds, all while maintaining excellent biosafety and biocompatibility. Our study offers a competitive and promising strategy for the development of a multifunctional synergistic antibacterial platform poised to effectively treat drug-resistant bacteria-infected cutaneous wounds.

Effect of Pericapsular Nerve Group Block with Different Concentrations and Volumes of Ropivacaine on Functional Recovery in Total Hip Arthroplasty: A Randomized, Observer-Masked, Controlled Trial.

Purpose: The pericapsular nerve group (PENG) block provides satisfactory postoperative analgesia without hampering motor function for total hip arthroplasty (THA); however, unexpected motor block has been observed clinically. It is unknown whether this motor block is related to the dose of ropivacaine. We aimed to conduct a prospective randomized trial to test whether reducing the volume or concentration of ropivacaine was better for less motor block after PENG block. Patients and Methods: Ninety-nine patients with fracture or femoral head necrosis scheduled for THA were randomly allocated to receive 20 mL 0.5% ropivacaine (Group A), 20 mL 0.25% ropivacaine (Group B), and 10 mL 0.5% ropivacaine (Group C). The primary outcome was the incidence of postoperative quadriceps motor block at 6 hours. Secondary outcomes were the incidence of postoperative quadriceps motor block at 0, 12, 24 and 48 hours; pain scores on the numeric rating scale (NRS) at all postoperative time points (0, 6, 12, 24, and 48 hours); the time to first walk; the incidence of rescue analgesia; side effects such as dizziness, ache, nausea, and vomiting; and patient satisfaction. Results: Compared with Group A, Group C resulted in a lower incidence of quadriceps motor block at 0 hours, 6 hours and 12 hours postoperatively (P < 0.05), while Group B only resulted in a lower incidence of motor block at 12 hours postoperatively (P < 0.05). No intergroup differences were found in terms of postoperative pain scores, the incidence of rescue analgesia, adverse events or patient satisfaction (P > 0.05). Conclusion: A higher incidence of motor blockade was observed when 20 mL of 0.5% ropivacaine was administered, which was mainly caused by the excessive volume. Therefore, we recommend performing PENG block with 10 mL 0.5% ropivacaine.

Protective effect of detoxified Rhus verniciflua stokes on human keratinocytes and dermal fibroblasts against oxidative stress and identification of the bioactive phenolics.

Oxidative stress due to the over-production of reactive oxygen species (ROS) is associated with human skin aging. This study was designed to identify the bioactive phenolics in detoxified Rhus verniciflua Stokes (DRVS) that may protect human skin against oxidative stress. Under oxidative stress caused by H2O2, the 40% (v/v) aqueous methanol extract of DRVS protected human keratinocytes in a dose-dependent manner. The expression of matrix metalloproteinase-1 (MMP-1) was also inhibited by the DRVS extract in human dermal fibroblasts-neonatal cells exposed to ultraviolet A. The major bioactive phenolics of DRVS were tentatively identified by LC/Q-TOF-ESI-MS/MS, and included gallic acid, 2-(ethoxymethoxy)-3-hydroxyphenol, fustin, a fustin isomer, tetragalloyl glucose, pentagalloyl glucose, fisetin, sulfuretin, a sulfuretin isomer, and butein. The results suggest that a DRVS extract may be effective in slowing skin aging through its antioxidative properties and by down-regulating MMP-1 expression. Further studies are needed to examine whether this effect would be mediated by the phenolics identified in this study.