Search

Background: Chlorhexidine (CHG) is a disinfectant commonly used in hospitals. However, it has been reported that the excessive use of CHG can cause resistance in bacteria to this agent and even to other clinical antibiotics. Therefore, new methods are needed to alleviate the development of CHG tolerance and reduce its dosage. This study aimed to explore the synergistic effects of CHG in combination with bacteriophage against CHG-tolerant Pseudomonas aeruginosa (P. aeruginosa) and provide ideas for optimizing disinfection strategies in clinical environments as well as for the efficient use of disinfectants. Methods: The CHG-tolerant P. aeruginosa strains were isolated from the First Affiliated Hospital of Wenzhou Medical University in China. The bacteriophage vB3530 was isolated from the sewage inlet of the hospital, and its genome was sequenced. Time-killing curve was used to determine the antibacterial effects of vB3530 and chlorohexidine gluconate (CHG). The phage sensitivity to 16 CHG-tolerant P. aeruginosa strains and PAO1 strain was detected using plaque assay. The emergence rate of resistant bacterial strains was detected to determine the development of phage-resistant and CHG-tolerant strains. Finally, the disinfection effects of the disinfectant and phage combination on the surface of the medical devices were preliminarily evaluated. Results: The results showed that (1) CHG combined with bacteriophage vB3530 significantly inhibited the growth of CHG-resistant P. aeruginosa and reduced the bacterial colony forming units (CFUs) after 24 h. (2) The combination of CHG and bacteriophage inhibited the emergence of phage-resistant and CHG-tolerant strains. (3) The combination of CHG and bacteriophage significantly reduced the bacterial load on the surface of medical devices. Conclusions: In this study, the combination of bacteriophage vB3530 and CHG presented a combined inactivation effect to CHG-tolerant P. aeruginosa and reduced the emergence of strains resistant to CHG and phage. This study demonstrated the potential of bacteriophage as adjuvants to traditional disinfectants. The use of bacteriophage in combination with commercial disinfectants might be a promising method for controlling the spread of bacteria in hospitals. [ABSTRACT FROM AUTHOR]

Purpose: Ureterocele has been hypothesized to be the risk factor for febrile urinary tract infections (F-UTIs) in patients with duplex collecting systems, but this has not been proved, and our goal was to assess the relation between ureterocele with duplex collecting systems and F-UTIs. Methods: We included individual-participant data from patients seen for complicated duplex collecting systems from 2010 to 2020 retrospectively followed. Those with using continuous low-dose antibiotic prophylaxis and incompletely duplicated systems were removed from the study. The participants were divided into two cohorts according to patients with or without ureterocele. The primary endpoint of this study was recurrent F-UTIs. Results: We analyzed medical reports of 300 patients, of which 75% were female. Among the 300 patients, F-UTIs developed in 111/159 (69.8%) patients in the ureterocele group and in 69/141 (48.9%) patients in the no-ureterocele group. Univariate analysis found no discernible difference except in grade of hydronephrosis between ureterocele group and no-ureterocele group. Moreover, Cox proportional regression analysis revealed that patients of duplex system ureterocele might be intrinsically more prone to develop F-UTIs (adjusted hazard ratio 1.894; 95% CI 1.412–2.542; p < 0.001). Conclusion: Among participants with duplex systems, the risk of recurrent F-UTIs in patients with ureterocele was higher than patients without it, and mini-invasive surgical correction should be considered at young age to reduce F-UTIs. [ABSTRACT FROM AUTHOR]

Despite available, advanced pharmacological and behavioral therapies, refractory chronic facial pain of different origins still poses a therapeutic challenge. In circumstances where there is insufficient responsiveness to pharmacological/behavioral therapies, deep brain stimulation should be considered as a potential effective treatment option. We performed an individual participant data (IPD) meta-analysis including searches on PubMed, Embase, and the Cochrane Library (2000–2022). The primary endpoint was the change in pain intensity (visual analogue scale; VAS) at a defined time-point of ≤3 months post-DBS. In addition, correlation and regression analyses were performed to identify predictive markers (age, duration of pain, frequency, amplitude, intensity, contact configuration, and the DBS target). A total of seven trials consisting of 54 screened patients met the inclusion criteria. DBS significantly reduced the pain levels after 3 months without being related to a specific DBS target, age, contact configuration, stimulation intensity, frequency, amplitude, or chronic pain duration. Adverse events were an infection or lead fracture (19%), stimulation-induced side effects (7%), and three deaths (unrelated to DBS—from cancer progression or a second stroke). Although comparable long-term data are lacking, the current published data indicate that DBS (thalamic and PVG/PAG) effectively suppresses facial pain in the short-term. However, the low-quality evidence, reporting bias, and placebo effects must be considered in future randomized-controlled DBS trials for facial pain. [ABSTRACT FROM AUTHOR]

Monolayer MoS2 has excellent optical properties, but its low optical absorption hinders its application in optical absorbers. To improve its absorption performance, we design an aperiodic multilayer structure with monolayer MoS2, the dielectric materials Si and SiO2 arranged by Kolakoski sequence, and achieve the perfect absorption in the visible wavelength range because of its omnidirectional reflectivity. By optimizing the thicknesses of SiO2 (db), Si (dc) and the repetition number (N) of the unit cell, the absorption of the aperiodic multilayer structure can be greatly improved at normal incidence. When N is 3, this aperiodic multilayer structure achieves high absorption of up to 98% in the wavelength range from 350 to 450 nm. As N increases to 5 or 7, the average absorption of this aperiodic multilayer structure exceeds 90% in the 350–600 nm wavelength range. In addition, we verify that the broadband and high absorption obtained in this aperiodic multilayer structure is robust against the angle of incidence and polarization of the incident wave. Our results suggest an alternative configuration with monolayer MoS2 to realize the broadband and perfect absorption, which is useful for future applications in solar cell or photodetectors. [ABSTRACT FROM AUTHOR]

Chronic pain (CP) represents a socio-economic burden for affected patients along with therapeutic challenges for currently available therapies. When conventional therapies fail, modulation of the affective pain matrix using reversible deep brain stimulation (DBS) or targeted irreversible thalamotomy by stereotactic radiosurgery (SRS) and magnetic resonance (MR)-guided focused ultrasound (MRgFUS) appear to be considerable treatment options. We performed a literature search for clinical trials targeting the affective pain circuits (thalamus, anterior cingulate cortex [ACC], ventral striatum [VS]/internal capsule [IC]). PubMed, Ovid, MEDLINE and Scopus were searched (1990–2021) using the terms "chronic pain", "deep brain stimulation", "stereotactic radiosurgery", "radioneuromodulation", "MR-guided focused ultrasound", "affective pain modulation", "pain attention". In patients with CP treated with DBS, SRS or MRgFUS the somatosensory thalamus and periventricular/periaquaeductal grey was the target of choice in most treated subjects, while affective pain transmission was targeted in a considerably lower number (DBS, SRS) consisting of the following nodi of the limbic pain matrix: the anterior cingulate cortex; centromedian-parafascicularis of the thalamus, pars posterior of the central lateral nucleus and internal capsule/ventral striatum. Although DBS, SRS and MRgFUS promoted a meaningful and sustained pain relief, an effective, evidence-based comparative analysis is biased by heterogeneity of the observation period varying between 3 months and 5 years with different stimulation patterns (monopolar/bipolar contact configuration; frequency 10–130 Hz; intensity 0.8–5 V; amplitude 90–330 μs), source and occurrence of lesioning (radiation versus ultrasound) and chronic pain ethology (poststroke pain, plexus injury, facial pain, phantom limb pain, back pain). The advancement of neurotherapeutics (MRgFUS) and novel DBS targets (ACC, IC/VS), along with established and effective stereotactic therapies (DBS–SRS), increases therapeutic options to impact CP by modulating affective, pain-attentional neural transmission. Differences in trial concept, outcome measures, targets and applied technique promote conflicting findings and limited evidence. Hence, we advocate to raise awareness of the potential therapeutic usefulness of each approach covering their advantages and disadvantages, including such parameters as invasiveness, risk–benefit ratio, reversibility and responsiveness. [ABSTRACT FROM AUTHOR]

Background: Contact patterns play a key role in the spread of respiratory infectious diseases in human populations. During the COVID-19 pandemic, the regular contact patterns of the population have been disrupted due to social distancing both imposed by the authorities and individual choices. Many studies have focused on age-mixing patterns before the COVID-19 pandemic, but they provide very little information about the mixing patterns in the COVID-19 era. In this study, we aim at quantifying human heterogeneous mixing patterns immediately after lockdowns implemented to contain COVID-19 spread in China were lifted. We also provide an illustrative example of how the collected mixing patterns can be used in a simulation study of SARS-CoV-2 transmission.Methods and Results: In this work, a contact survey was conducted in Chinese provinces outside Hubei in March 2020, right after lockdowns were lifted. We then leveraged the estimated mixing patterns to calibrate a mathematical model of SARS-CoV-2 transmission. Study participants reported 2.3 contacts per day (IQR: 1.0-3.0) and the mean per-contact duration was 7.0 h (IQR: 1.0-10.0). No significant differences in average contact number and contact duration were observed between provinces, the number of recorded contacts did not show a clear trend by age, and most of the recorded contacts occurred with family members (about 78%). The simulation study highlights the importance of considering age-specific contact patterns to estimate the COVID-19 burden.Conclusions: Our findings suggest that, despite lockdowns were no longer in place at the time of the survey, people were still heavily limiting their contacts as compared to the pre-pandemic situation. [ABSTRACT FROM AUTHOR]

Purpose: To compare the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses. Methods: The clinical characteristics corresponding to pediatric urolithiasis patients that had undergone exome sequencing at our hospital between January 2016 and May 2021 were collected. Genetic analysis results were used to separate patients into positive and negative molecular diagnosis groups. Multivariate logistic regression analyses adjusted for visiting age, sex, ethnicity, province, and body mass index were used to compare differences in medical history, diagnostic imaging findings, and renal function between individuals with and without molecular diagnoses. Results: In total, 194 patients with pediatric urolithiasis of unknown etiology underwent exome sequencing and were included in the present study, of whom 63 obtained urolithiasis-related molecular diagnoses. Relative to cases without a molecular diagnosis, those with a positive molecular diagnosis were more likely to be associated with a positive family history (OR 2.84, 95% CI 1.29–6.29, p = 0.008), consanguineous parents (OR 24.7, 95% CI 1.34–454, p = 0.002), early onset (OR 1.26, 95% CI 1.09–1.45, p < 0.001), nephrocalcinosis (OR 10.6, 95% CI 3.06–36.6, p < 0.001), cast stone (OR 18.9, 95% CI 4.40–81.1, p < 0.001), multiple stones (OR 13.9, 95% CI 6.39–30.2, p < 0.001), bilateral stones (OR 7.04, 95% CI 3.47–14.2, p < 0.001), a lower estimated glomerular filtration rate (OR 1.17, 95% CI 1.07–1.28, p < 0.001), and chronic kidney disease (OR 26.9, 95% CI 1.42–526, p < 0.001). Conclusion: A positive family history, consanguineous parents, early onset, nephrocalcinosis, severe stone burden, and impaired renal function are signals of concern that are suggestive of inherited urolithiasis. [ABSTRACT FROM AUTHOR]

Atomically precise palladium nanoclusters show great potential applications in the field of catalysis owing to its ultrasmall size and precise structure. This work, we report the mesoporous silica nanoparticles (MSNs) supported [Pd3Cl(PPh3)3(PPh2)2]Cl catalysts (denoted as Pd3Cl/MSNs) for the reduction of 4‐nitrophenol and Heck coupling reactions of iodobenzene and styrenes. High uniform MSNs, with average diameter ≈110 nm, were prepared by sol–gel method, followed by Pd nanoclusters immobilization into the pore of MSNs. The MSNs supported Pd nanoclusters were well characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT‐IR), and diffuse reflectance optical spectrum. The results indicated that Pd3Cl nanoclusters after immobilized into the pores of MSNs are intact and possess good dispersibility. The catalytic performance of as‐prepared nanocomposites was evaluated by the reduction of 4‐nitrophenol and Heck reactions. The 4‐nitrophenol could be completely conversion to 4‐aminophenol within 6 min. Meanwhile, the as‐prepared Pd3Cl/MSNs exhibit excellent catalytic performance in the Heck reactions between iodobenzenes and styrenes. The high catalytic activity of Pd3Cl/MSNs could be attributed to the large surface area and unique geometric structure of as‐prepared Pd nanoclusters. More importantly, the catalysts could be easily recycled by centrifugation and shows excellent reusability. [ABSTRACT FROM AUTHOR]

Regulators of G protein signaling (RGSs) are proteins that negatively regulate G protein signal transduction. In this study, seven putative RGSs were characterized in the nematode-trapping (NT) fungus, Arthrobotrys oligospora. Deleting Rgs genes significantly increased intracellular cAMP levels, and caused defects in mycelia growth, stress resistance, conidiation, trap formation, and nematocidal activity. In particular, the ΔAoFlbA mutant was unable to produce conidia and traps. Transcriptomic analysis showed that amino acid metabolic and biosynthetic processes were significantly enriched in the ΔAoFlbA mutant compared to WT. Interestingly, Gas1 family genes are significantly expanded in A. oligospora and other NT fungi that produce adhesive traps, and are differentially expressed during trap formation in A. oligospora. Disruption of two Gas1 genes resulted in defective conidiation, trap formation, and pathogenicity. Our results indicate that RGSs play pleiotropic roles in regulating A. oligospora mycelial growth, development, and pathogenicity. Further, AoFlbA is a prominent member and required for conidiation and trap formation, possibly by regulating amino acid metabolism and biosynthesis. Our results provide a basis for elucidating the signaling mechanism of vegetative growth, lifestyle transition, and pathogenicity in NT fungi. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of inherited causes in an early onset urolithiasis cohort and each metabolic subgroup. Methods: A retrospective analysis of both metabolic and genomic data was performed for the first 105 pediatric urolithiasis patients who underwent exome sequencing at our hospital from February 2016 to October 2018. Measurements included the diagnostic yield of exome sequencing in the entire cohort and each metabolic subgroup (hyperoxaluria, hypocitraturia, hypercalciuria, hyperuricosuria and cystine stone subgroups). The conformity between molecular diagnoses and metabolic evaluation was also evaluated. Results: The present study involved a cohort of 105 pediatric patients with urolithiasis, from which diagnostic variants were identified in 38 patients (36%), including 27 primary hyperoxaluria and 11 cystinuria. In the metabolic subgroup analyses, 41% hyperoxaluria cases were primary hyperoxaluria caused by monogenic defects, and 100% of the causes of cystine stones could be explained by monogenic defects. However, no appropriate inherited causes were identified for hypocitraturia, hypercalciuria, or hyperuricosuria in the cohort. A high conformity (100%) was obtained between the molecular diagnoses and metabolic evaluation. Conclusion: Exome sequencing in a cohort of 105 pediatric patients with urolithiasis yielded a genetic diagnosis in 36% of cases and the molecular diagnostic yield varies substantially across different metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Keywords: brain stimulation; chronic pain disorders; neuroinflammation; cytokine; adipokine; brain-immune communication EN brain stimulation chronic pain disorders neuroinflammation cytokine adipokine brain-immune communication 364 3 03/30/22 20220301 NES 220301 Chronic pain is characterized by an impaired functional state (pain, mood, sleep, cognition, and metabolism) affecting different brain networks relevant for pain perception and neural pain processing. Brain stimulation, neuroinflammation, cytokine, brain-immune communication, chronic pain disorders, adipokine. [Extracted from the article]

Although mixed land use is an important way to improve land-use efficiency and stimulate socioeconomic vitality, there are few systematic analyses of mixed land use in rural settlements. This paper proposes the connotation and measurements of mixed land use in rural settlements, considering both land-use diversity and compatibility. Case studies of Tangwei village (a tourist village), Guxia village (a commercial village), and Fulong village (an industrial village) in Dongguan City, Pearl River Delta, China, are chosen to analyze the characteristics of mixed land use in different types of rural settlements using field research, POI data capture, GIS, and remote sensing techniques. The results indicate that: (1) In 1978, 2005, and 2020, the degree of mixed land use in the rural settlement of Tangwei village was 0.68, 0.84, and 0.96, respectively, reflecting an increase of 41.17%; in Guxia village, it was 0.69, 0.86, and 0.84, respectively, growing and then declining, yielding a total increase of 21.73%; in Fulong village, it was 0.74, 0.82, and 0.89, respectively, reflecting an increase of 20.27%. (2) In 1978, 2005, and 2020, the land-use diversity of Tangwei village was 0.44, 0.94, and 0.92, respectively, representing a 109% improvement; land-use compatibility was 0.68, 0.72, and 0.96, respectively, with an increase of 41.17%. The land-use diversity of Guxia village was 0.46, 0.76, and 0.78, respectively, with an increase of 69.57%; land-use compatibility climbed by 24.64% from 0.69 to 1 to 0.84. The land-use diversity of Fulong village was 0.53, 0.83, and 0.88, respectively, which increased by 66.03%; land-use compatibility was 0.74, 0.81, and 0.89, respectively, which increased by 20.27%. (3) The mixed land use of Tangwei village is primarily influenced by policy support, resource endowment, and industrial foundation. The primary drivers of Guxia village are policy support, geographic location, and industrial foundation. Policy support, resource endowment, and industrial foundation are the most critical factors in Fulong village. Ultimately, land-use diversity and compatibility determine the mixed land use of rural settlements. This study offers suggestions for village planning, rural industrial development, and enhancing the living environment in China. • A conceptual framework of mixed land use in rural settlements was established. • The characteristics and driving forces of mixed land-use evolution in rural settlements were revealed. • Considering land-use diversity and compatibility improved the measurement of mixed land use. • Mixed land use of rural settlements can promote the coordinated improvement of villagers' living conditions and rural industrial development. [ABSTRACT FROM AUTHOR]

Objectives: Infantile spasm (IS) is an epileptic encephalopathy with ongoing neurological damage due to seizures and epileptiform abnormalities. Epilepsy surgery is considered for children refractory to drug therapy, especially when there is a focal brain lesion. In this study, we investigated the feasibility and efficacy of intraventricular stereotactic electroencephalography (SEEG) and laser ablation for the treatment of IS children with focal brain lesions. Methods: We performed the first reported study using ventriculoscopic laser ablation to treat IS. Seven IS children with drug‐resistant epilepsy and definite encephalomalacia on brain magnetic resonance imaging scan were included in this study. Ablation was performed after confirmation of epileptiform discharges by SEEG under the surveillance of ventriculoscope. Results: The median follow‐up time for the cohort was 3.1 years and 86% (6/7) of the children had an Engel class ≤III epilepsy at the final follow‐up. Five (71%) children had a reduction in seizure medication usage, and the other two were on the same amount as preablation. None of the children experienced serious new neurological deficits. Laser ablation might result in seizure freedom by destroying the local brain network and blocking the spread of abnormal discharges. Conclusions: Intraventricular SEEG and laser ablation was feasible and effective for the treatment of IS. Further studies are warranted. [ABSTRACT FROM AUTHOR]

We also summarized some suggestions and concerns of this study for discussion: (1) this study can use genotype imputation to estimate unobserved genotypes, which may help researchers find more statistically significant SNP loci [[1]]. Dear Editor, Considering genetic factors, urolithiasis may be a monogenic disease or a polygenic disease. [Extracted from the article]

The bacteriophage vB8388 can lyse multi-drug resistant Klebsiella oxytoca strain FK-8388 and maintain stability in a wide range of temperatures (from 4 °C to 80 °C) and pHs (3–11). Bioinformatics analysis showed that vB8388 is a linear double-stranded DNA virus that is 39,750 long with 50.65% G + C content and 44 putative open reading frames (ORFs). Phage vB8388 belongs to the family Autographviridae and possesses a non-contractile tail. The latency period of vB8388 was approximately 20 min. The combination of phage vB8388 and gentamicin, amikacin, or tobramycin could effectively inhibit the growth of K. oxytoca strain FK-8388, with a decrease of more than 4 log units within 12 h in vitro. Phage vB8388 showed a strong synergistic effect with gentamicin that could enhance the anti-biofilm effect of vB8388. The phage + gentamicin combination also showed synergy in vivo in the larval infection model of Galleria mellonella. In conclusion, the findings of this study suggest the potential of phage + antibiotic combination therapy to be used as an alternative therapeutic approach for treating infectious diseases caused by multidrug-resistant bacteria. • A lytic bacteriophage against a multidrug-resistant Klebsiella oxytoca strain. • Synergistic effect between bacteriophage and aminoglycosides in vitro. • The mature biofilm of K. oxytoca was significantly eradicated in the phage + gentamicin combination treatment groups. • Gentamicin and amikacin showed synergistic effects with phage in vivo. [ABSTRACT FROM AUTHOR]

The continued rise of Klebsiella pneumoniae resistance to antibiotics is precipitating a medical crisis. Bacteriophages have been hailed as one possible therapeutic option to enhance the efficacy of antibiotics. This study describes the genomic characterization and biological property of a new bacteriophage vB_1086 and its potential for phage therapy application against Klebsiella pneumoniae. In our study, the double-layer agar plate method isolated a lytic bacteriophage named vB_1086. Besides, we analyzed its biological characteristics and genetic background. Then the antibacterial ability of the bacteriophage vB_1086 combined with antibiotics were analyzed by the combined checkerboard method. The impact on the formation of biofilms was analyzed by crystal violet staining method. vB_1086 is a lytic bacteriophage with stable biological characteristics and clear genetic background, showing good antibacterial activity in combination with ceftriaxone, and the combination of phage and meropenem can effectively inhibit the formation of biofilm. Besides, the combination of bacteriophage and antimicrobials can effectively alleviate the generation of bacterial resistance and reduce the dosage of antimicrobials. vB_1086 is a novel phage. To some extent, these results provide valuable information that phage vB_1086 can be combined with antibiotics to reduce the dosage of antimicrobials and alleviate the generation of bacterial resistance. • This study found a new bacteriophage vB_1086(GenBank accession number: OL865411), and described the genomic characterization and biological property of it. • The combination of bacteriophage vB_1086 and ceftriaxone reduce the dosage of antimicrobials and alleviate the generation of bacterial resistance. • The combination of bacteriophage vB_1086 and meropenem could inhibit the biofilm formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Assessing variants in non-canonical splicing sites is important during the process of exome sequencing-based primary hyperoxaluria diagnosis. • Capture sequencing-based copy number variant detection should be conducted in patients undergoing exome sequencing to diagnose suspected primary hyperoxaluria. • Exome sequencing will become a standard approach to diagnosing primary hyperoxaluria in pediatric urolithiasis patients. Next generation sequencing-based exome sequencing can be used to identify genetic abnormalities in patients believed to be suffering from primary hyperoxaluria. We outline our efforts to improve the diagnostic capacity of exome sequencing for these patients. We conducted a retrospective analysis of exome sequencing data from 77 pediatric urolithiasis patients with hyperoxaluria of unknown origin. Canonical exome sequencing analysis was performed to identify pathogenic variants in three known primary hyperoxaluria-related genes (AGXT , GRHPR , HOGA1) as per the guidelines of the American College of Medical Genetics. Then, extended exome sequencing analyses of 5′-untranslated region, non-canonical splicing site and copy number variant were performed on patients with negative diagnostic results in these three genes. Canonical exome sequencing analyses led to the diagnosis of primary hyperoxaluria in 20/77 (26%) patients, including eight, four, and eight patients diagnosed with type 1, 2 and 3 primary hyperoxaluria, respectively. Non-canonical splicing site analyses discovered a pathogenic variant in the HOGA1 gene, which led to the diagnosis of six additional patients with type 3 primary hyperoxaluria, while copy number variant analyses from exome sequencing data identified a 1.8 kb copy number loss that impacted the AGXT gene, resulting in the diagnosis of an additional type 1 primary hyperoxaluria case. Extended non-canonical splicing site and copy number variant analyses improve the diagnostic yield of canonical exome sequencing analysis for primary hyperoxaluria from 26% (20/77) to 35% (27/77) in 77 pediatric urolithiasis patients with hyperoxaluria. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. Methods: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0–2 at the 6-month follow-up. Results: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P =.017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P =.000). Conclusions: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. Trial Registration: ClinicalTrials.gov Identifier: NCT02811614. [ABSTRACT FROM AUTHOR]

Although radiotherapy is the most effective treatment modality for brain tumors, it always injures the central nervous system, leading to potential sequelae such as cognitive dysfunction. Radiation induces molecular, cellular, and functional changes in neuronal and glial cells. The hippocampus plays a critical role in learning and memory; therefore, concerns about radiation‐induced injury are widespread. Multiple studies have focused on this complex problem, but the results have not been fully elucidated. Naked mole rat brains were irradiated with 60Co at a dose of 10 Gy. On 7 days, 14 days, and 28 days after irradiation, hippocampi in the control groups were obtained for next‐generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. Venn diagrams revealed 580 differentially expressed genes (DEGs) that were common at different times after irradiation. GO and KEGG analyses revealed that the 580 common DEGs were enriched in molecular transducer activity. In particular, CACNA1B mediated regulatory effects after irradiation. CACNA1B expression increased significantly after irradiation. Downregulation of CACNA1B led to a reduction in apoptosis and reactive oxygen species levels in hippocampal neurons. This was due to the interaction between CACNA1B and Nrf2, which disturbed the normal nuclear localization of Nrf2. In addition, CACNA1B downregulation led to a decrease in the cognitive functions of naked mole rats. These findings reveal the pivotal role of CACNA1B in regulating radiation‐induced brain injury and will lead to the development of a novel strategy to prevent brain injury after irradiation. [ABSTRACT FROM AUTHOR]

Effective 3D shape retrieval and recognition are challenging but important tasks in computer vision research field, which have attracted much attention in recent decades. Although recent progress has shown significant improvement of deep learning methods on 3D shape retrieval and recognition performance, it is still under investigated of how to jointly learn an optimal representation of 3D shapes considering their relationships. To tackle this issue, we propose a multi-scale representation learning method on hypergraph for 3D shape retrieval and recognition, called multi-scale hypergraph neural network (MHGNN). In this method, the correlation among 3D shapes is formulated in a hypergraph and a hypergraph convolution process is conducted to learn the representations. Here, multiple representations can be obtained through different convolution layers, leading to multi-scale representations of 3D shapes. A fusion module is then introduced to combine these representations for 3D shape retrieval and recognition. The main advantages of our method lie in 1) the high-order correlation among 3D shapes can be investigated in the framework and 2) the joint multi-scale representation can be more robust for comparison. Comparisons with state-of-the-art methods on the public ModelNet40 dataset demonstrate remarkable performance improvement of our proposed method on the 3D shape retrieval task. Meanwhile, experiments on recognition tasks also show better results of our proposed method, which indicate the superiority of our method on learning better representation for retrieval and recognition. [ABSTRACT FROM AUTHOR]

Lithium cobalt oxide (LiCoO2) is one of the most commercially successful cathode materials and has attracted much attention from researchers since its discovery. However, an increase in cut-off voltage generates problems such as structural damage and detrimental side reactions. Under this premise, a layer of LiTaO3 coating is sputtered on the surface of the LiCoO2 electrode by magnetron sputtering, which aims to inhibit the structural damage and the occurrence of side reactions under high voltage. Meanwhile, the ionic conductor layer of LiTaO3 can also promote the transmission process of Li+ and improve the power density. The results show that the capacity retention rate of the MS-2 h (magnetron sputtering for 2 hours) electrode is 86.6% at 0.5C for 100 cycles in a voltage range of 3.0–4.6 V, and the capacity of 91 mA h g−1 is achieved at 3C. The cycling stability of the electrode is also effectively improved at high temperature, and the capacity retention rate was 40.9% after 100 cycles at 50 °C. This work proves that the coating of LiTaO3 on the electrode surface by magnetron sputtering can effectively inhibit the damage of the electrode structure and the occurrence of side reactions during cycling and can promote the transmission of lithium ions. [ABSTRACT FROM AUTHOR]

Adults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. We conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter − former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. During a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, −96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. Among middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes. • High visit-to-visit HbA1c variability was associated with an increased dementia risk. • High visit-to-visit HbA1c variability was associated with low hippocampal volume. • Monitoring HbA1c fluctuation is of great importance in adults without diabetes. [ABSTRACT FROM AUTHOR]

As a diagnostic biomarker, the detection of circular RNA (circRNA) is vital for the early screening of bladder cancer. Usually, the low abundance of circRNA in clinic samples results in the necessarily complicated extraction before detection. In this work, a tetrahedron supported CRISPR/Cas13a cleavage has been explored for direct electrochemical detection of circRNA in urine from bladder cancer. CRISPR/Cas13a system has been reasonably designed to recognize the characteristic back-splice junction site of circRNA. The activated CRISPR/Cas13a by circRNA can cleave uracil bases composed of DNA tetrahedron immobilized on the surface of gold electrode, resulting in the breakage of DNA tetrahedron and the release of electrochemical active molecule methylene blue. By virtue of highly catalytic efficiency of CRISPR/Cas13a and rigid structure of tetrahedron, the developed electrochemical biosensor can directly detect circRNA in 25 μL urine sample with the lowest detection limit of 0.089 fM and linear detection range from 10 fM to 50 nM in less than 10 min, so as to avoid complicated extraction process and benefit for on-site detection. [ABSTRACT FROM AUTHOR]

• Leptin and its receptor ObR play a critical role in Parkinson's disease etiology and progression via its neuroinflammatory properties. • Experimental work is needed to further elaborate leptin signaling in disease onset and progression. • Large-scale in-human studies of leptin and other adipokines taking into account multiple covariates are warranted. • In view of the dual character of leptin (neuroprotective versus pro-inflammatory), other adipokines (e.g., ghrelin, adiponectin) may represent better targets for PD. An increasing body of experimental evidence implicates a relationship between immunometabolic deterioration and the progression of Parkinson's disease (PD) with a dysregulation of central and peripheral neuroinflammatory networks mediated by circulating adipokines, in particular leptin. We screened the current literature on the role of adipokines in PD. Hence, we searched known databases (PubMed, MEDLINE/OVID) and reviewed original and review articles using the following terms: "leptin/ObR", "Parkinson's disease", "immune-metabolism", "biomarkers" and "neuroinflammation". Focusing on leptin, we summarize and discuss the existing in vivo and in vitro evidence on how adipokines may be protective against neurodegeneration, but at the same time contribute to the progression of PD. These components of the adipose brain axis represent a hitherto underestimated pathway to study systemic influences on dopaminergic degeneration. In addition, we give a comprehensive update on the potential of adjunctive therapeutics in PD targeting leptin, leptin-receptors, and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanisms of action and the value of central and peripheral adipose-immune-metabolism molecular phenotyping in order to develop and validate the differential roles of different adipokines as potential therapeutic target for PD patients. [ABSTRACT FROM AUTHOR]

The other authors did not respond to any correspondence from the editor or publisher about the wording of this retraction notice. Retraction to: J Nanobiotechnol (2018) 16:66 https://doi.org/10.1186/s12951-018-0397-3 The Editors-in-Chief have retracted this article due to concerns with Figure 1. [Extracted from the article]

As TNFAIP8 plays an important role in the development of cancer, several studies have analyzed the relationship between potential functional polymorphic loci of the TNFAIP8 gene and cancer risk. However, some results were inconsistent. Therefore, the current study aims to systematically assess the relationship between these genetic polymorphisms and cancer risk using a meta-analysis approach. Relevant studies were obtained from CNKI, Embase, Web of Science, and PubMed databases. RevMan software was used to conduct data analysis. The combined analysis containing four studies with 2786 cancer patients and 2550 control individuals indicated that rs11064 polymorphism was not associated with cancer risk. The pooled analysis containing three studies with 950 cancer patients and 1036 control individuals showed that rs1045241 polymorphism was associated with cancer risk in the heterozygous model (CT vs. CC: OR = 1.34, 95%CI = 1.10‐1.62, Pz=0.003) and dominant model [(TT + CT) vs. CC: OR = 1.38, 95% CI = 1.15-1.66, Pz=0.0006], but not in other models. The pooled analysis containing two studies 436 cancer patients and 479 control individuals showed that rs1045242 polymorphism was associated with cancer risk in the heterozygous model (AG vs. AA: OR = 1.52, 95%CI = 1.14-2.03, Pz=0.005), dominant model [(GG + AG) vs. AA: OR = 1.56, 95% CI = 1.18-2.07, Pz=0.002] and allelic model (G vs. A: OR = 1.48, 95%CI = 1.16-1.90, Pz=0.002). In conclusion, the current findings suggest that the rs1045241 and rs1045242 polymorphisms located on the TNFAIP8 gene were associated with cancer risk in Chinese population, and may serve as valuable genetic susceptibility markers. [ABSTRACT FROM AUTHOR]

Background and Objectives: To evaluate the effectiveness of insulin addition to the total nutrition admixture (TNA) for glycemic control among patients with gastric cancer (GC) receiving supplementary parenteral nutrition (SPN) after gastrectomy.Methods and Study Design: A retrospective cohort study was conducted among 208 noncritical ill patients who underwent gastrectomy for GC from 2017 to 2019 at a tertiary teaching hospital in Lanzhou, China. All the included patients received individualized SPN and enteral nutrition treatment after gastrectomy. The patients were randomly divided into insulin and noninsulin groups based on the TNA composition. Blood glucose (BG) measurements, glycemic fluctuation, and hypoglycemia incidence during SPN were compared between the two groups. The postoperative comprehensive complications index (CI) and infections were compared according to insulin regimen and postoperative glycemic status.Results: The mean BG was significantly lower and fluctuated less in the insulin group than in the noninsulin group (p<0.05). One unit of insulin per 6 g of parenteral nutrition glucose addition to TNA did not increase hypoglycemia incidence (p>0.05). Comparing CI and the infection rate, no significance was observed between the insulin and noninsulin groups, but a higher postoperative CI was observed in patients with hyperglycemia than in euglycemic patients (p<0.05).Conclusions: Appropriate insulin addition to TNA has an overall positive effect on glycemic management in patients with noncritical GC who received SPN after gastrectomy. Postoperative glycemic status was associated with the incidence of relevant complications. Further research is needed for conclusive recommendations. [ABSTRACT FROM AUTHOR]

In recent years, several case-control studies have explored the association between the rs7763881 locus polymorphism of the HULC gene and cancer risk, however, the findings have been inconsistent. Therefore, a meta-analysis was conducted to clarify the association. Relevant case-control studies were obtained from CNKI, Embase, Web of Science and PubMed databases. RevMan software was used to perform data analysis. A total of 8 case-control studies containing 4036 cases and 5286 controls were included in the current meta-analysis. The overall analysis results showed no significant association between the rs7763881 locus polymorphism and cancer risk. However, stratified analysis based on cancer type showed that the rs7763881 locus polymorphism was associated with the decreased risk of hepatocellular cancer, colorectal cancer and esophageal cancer. In conclusion, the current findings suggest that the rs7763881 polymorphic loci located on the HULC gene may serve as a biomarker for determining an individual's risk of hepatocellular cancer, colorectal cancer and esophageal cancer. [ABSTRACT FROM AUTHOR]

The accurate detection of immune checkpoint molecules on the surface of tumor cells is of great significance for immunotherapy. Herein, we propose a method based on cellular interface supported cascade signal amplification mediated by CRISPR/Cas13a system for in situ analysis of immune checkpoint molecules on bladder cancer cells. CD47 and EpCAM on bladder cancer cells can be sensitively monitored through T7 transcription amplification, CRISPR/Cas13a system and HCR triple signal amplification. Moreover, the established method can specifically differentiate EpCAM and CD47 positive bladder cancer cells and well serve for the evaluation of two kinds of membrane protein inhibitors. In a word, the method we proposed can successfully realize in situ analysis of immune checkpoint molecules on bladder cancer cells for guiding immunotherapy. • Immune checkpoint molecules can be analyzed in situ by our established new method. • The method is based on cellular interface supported cascade signal amplification. • Triple signal amplification is firstly explored based on CRISPR/Cas13a system. [ABSTRACT FROM AUTHOR]

[Display omitted] • Double enzymatic hydrolysis combined with IL-US improved DPP-IV inhibitory activity. • IL-US pretreatment induced the exposure of active sites and hydrophobic amino acids. • IL-US pretreatment enhanced the gastrointestinal stability of collagen peptides. • Five new antidiabetic peptides were identified via LC-MS/MS and molecular docking. • The identified GPVGPPG sequence might be the most effective DPP-IV inhibitor. The present study focused on the effects of different preparation conditions on the activity and peptide sequence identification of DPP-IV inhibitory peptides based on discarded cowhide collagen and its regulation mechanism. The highest DPP-IV inhibitory activity (IC 50 of 3.04 ± 0.13 mg/mL) was obtained by the combination of double enzymatic hydrolysis (papain and compound protease) and optimized IL-US (ultrasound-assisted ionic liquids) pretreatment. The optimal pretreatment condition for ultrasonic power, ultrasonic time, ionic liquid/collagen ratio, and collagen concentration were 389 W, 25 min, 0.7, and 0.3 %, respectively. IL-US pretreatment induced the exposure of active sites and hydrophobic amino acids of collagen peptide, promoted the partial transformation of β-sheet to β-turn, and enhanced the stability of gastrointestinal digestion. Seven new peptides with DPP-IV inhibitory ability were identified. Importantly, further molecular docking showed that five peptides (GPVG, FGPGP, APGGAP, GPPGPT, and GPVGPPG) were proposed to be antidiabetic peptides from cowhide collagens. [ABSTRACT FROM AUTHOR]

Interactions between coal matrix and organics are vital for adsorption [1] , surfactant adsorption on lignite [2-5] , and solid–liquid separation of coal slurry [6-10]. Herein, for studying the interaction between hydrophobic surface (coal surface) and small molecules (organics), we measured interactions between organics [nitro and phenyl, pyridine, phenyl, alkyl chain (hexyl) or cycloalkyl (hexyl)] and the coal matrix (liptinite or inertinite) using atomic force microscopy. The strength of interaction followed the order: nitro and phenyl > pyridine > phenyl > alkyl chain (hexyl) > cycloalkyl (hexyl), and liptinite > inertinite. The liptinite has a greater hydrophobicity than inertinite, the greater the attraction force. The lignite surface and coal slurry were modified in an aqueous solution using five surfactants (dodecyl trimethyl ammonium chloride, DTAC; hexadecyl trimethyl ammonium chloride, CTAC; octadecyl trimethyl ammonium chloride, STAC; hexadecyl dimethyl benzyl ammonium chloride, HDBAC; and cetyl pyridine chloride, CPC). Subsequently, the moisture adsorption on treated lignite coal surface and the sedimentation of the treated tails was compared to characterize hydrophobic modifications which showed the order of CTAC > HDBAC > DTAC > CPC > STAC. Thus, the interaction between coal surface and organics needs to consider two rules: 1) The desolvation or the hydrophobic property of the coal surface; 2) The VDW force of the organics. The nature of the difference between rules No. 1 and 2 is that with the size of hydrophobic molecules increased to a surface, the H-bond structure between water molecules in the around would change a lot, which formats great hydrophobic property or desolvation. Interaction between organic reagents and coal reveals the mechanism of restraining moisture reabsorption of lignite and solid–liquid separation of coal slurry by organics. [ABSTRACT FROM AUTHOR]

Aiming to extend the chemical space of existing FXR agonists, we performed a SAR study based on auraptene, and resulted in the discovery of novel FXR agonist 14. [Display omitted] • The chemical space of FXR agonist was extended based on auraptene. • The unstable coumarin and geraniol scaffolds of auraptene were optimized. • Compound 14 has been identified benefit by molecular simulation. • Compound 14 exhibited nearly fourfold higher activity than auraptene. • Compound 14 exerts better therapeutic effect than auraptene in APAP-induced liver injury. Farnesoid X receptor (FXR) has been considered as an attractive target for metabolic disorder and liver injury, while many current FXR agonists suffer from undesirable side effects, such as pruritus. Therefore, it is urgent to develop new structure types different from current FXR agonists. In this study, a series of structural optimizations were introduced to displace the unstable coumarin and geraniol scaffolds of auraptene (AUR), a novel and safe FXR agonist. All of these efforts led to the identification of compound 14, a potent FXR agonist with nearly fourfold higher activity than AUR. Molecular modeling study suggested that compound 14 fitted well with binding pocket, and formed the key ionic bond with His291 and Arg328. In acetaminophen-induced acute liver injury model, compound 14 exerts better therapeutic effect than that of AUR, which highlighting its pharmacological potential in the treatment of drug-induced liver injury. [ABSTRACT FROM AUTHOR]