Design of a water-soluble transmembrane receptor kinase with intact molecular function by QTY code.

Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.

Widening of narrow urethral plates with lateral skin in TIP hypospadias repair: single center series.

BACKGROUND: To compare the outcomes of hypospadias repair using tubularized incised plate (TIP) urethroplasty and modified TIP with lateral skin to widen the urethral plate (WTIP). MATERIALS AND METHODS: Data were obtained from pre-pubertal boys who underwent primary hypospadias repair between May 2018 and July 2023. The cases were divided into two groups; one group underwent TIP with urethral plate ≥ 6 mm width and the other group with urethral plate width < 6 mm underwent WTIP. WTIP urethroplasty was performed by widening incisions on the outer margins of the urethral plate to incorporate penile and glandular skin lateral to the urethral plate to facilitate tubularization. Complication rates and urinary functions were compared. RESULTS: A total of 157 patients were enrolled in this study. Eighty-eight cases with narrow urethral plate were subjected to WTIP urethroplasty, and the rest were subjected to TIP urethroplasty. The preoperative glans width in WTIP group was less than that in TIP group (P < 0.001), and 44.3% had midshaft meatus in WTIP group compared to 17.4% in TIP group (P < 0.001). However, the incidences of postoperative complications (17.6% vs. 21.6%, P = 0.550) were not statistically different between the TIP and WTIP groups. In addition, both groups did not differ significantly in postoperative uroflowmetry assessment. CONCLUSIONS: The described technique helps to create an adequately caliber aesthetic neomeatus and facilitates tubularization, especially in hypospadias with a narrow urethral plate. Our data suggest that augmentation of a narrow urethral plate with WTIP has a similar surgical outcome to that of the TIP procedure in patients with a wide urethral plate.

Effect of S⋯π interactions on the charge transport properties of the DPP framework.

In this work, we designed and synthesized two similar π-conjugated molecules, N-alkyl (DPP-R) and N-aryl (DPP-B), to comparatively explore the S⋯π interactions using a scanning tunneling microscopy-based break junction (STM-BJ) technique. The conductance results of the STM-BJ experiments indicated that DPP-R has a 66% greater conductance (G) than DPP-B. Combined with molecular simulations, it was demonstrated that the presence of S⋯π interactions led to a certain degree of orbital overlap of the highest occupied molecular orbital (HOMO), and created a favorable channel for electron transport in the DPP-B junction.

QTY code designed antibodies for aggregation prevention: A structural bioinformatic and computational study.

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water-solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the ß-sheets. Through the structure-based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild-type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen-binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.

Laparoscopic extraction of a urethral self-inflicted needle from pelvis in a boy: a case report.

Introduction: Self-insertion of foreign bodies in the urethra is an infrequent occurrence in children, and their management aims to minimize urethral morbidity. Endoscopic removal presents a significant challenge, particularly in boys. Currently, there are few reports on laparoscopic management of urethral foreign bodies that have migrated to the pelvic cavity. Case description: An 11-year-old boy presented to the emergency department with complaints of increased frequency of micturition and dysuria. A sharp sewing needle was discovered lodged in the posterior urethra mucosa during cystoscopy. Attempts to remove the needle using an endoscopic grasping forceps were unsuccessful due to the forceps' weak biting power. During a digital rectal examination, the needle migrated into the pelvic region, wedged between the prostatic urethra and the rectal ampulla. After careful inspection of the peritoneal reflection over the fundus of the bladder, the needle was identified and successfully removed through laparoscopy without any complications. Psychiatric counseling was advised for this patient, who was in good condition during an 8-week follow-up. Conclusions: Our case demonstrates the first recorded use of laparoscopy to remove a self-inserted urethral needle that had migrated into the pelvic region, after failed attempts at endoscopic extraction. Future cases may benefit from considering laparoscopic interventions for similar circumstances.

Case report: Minimally invasive removal of a dislodged thoracoamniotic shunt with an integral cystoscope in a preterm infant.

Introduction: Fetal pleural effusion is a rare condition that is associated with significant mortality. Although the insertion of fetal thoracoamniotic shunts can improve perinatal outcomes, there are several associated complications, such as intrathoracic dislodgement of the shunts. The optimal neonatal treatment for retained shunts remains uncertain. Case Description: A male infant was born at 32 weeks of gestation. He had antenatal hydrothorax that was detected at 27 weeks of gestation and was managed by intrauterine thoracoamniotic shunting. However, the shunt catheter dislodged into the fetal chest, which caused reaccumulated pleural effusion and respiratory distress requiring ventilatory support after birth. After the patient's condition stabilized, minimally invasive removal of the retained catheter was performed on day 17 of life using an integral pediatric cystoscope via a 3-mm thoracic incision. The procedure took approximately 5 min. The postoperative course was uneventful, and the patient, who was discharged 39 days postnatally, is thriving at the 6-month follow-up. Conclusions: We present a novel and effective approach to the management of an intrathoracic shunt using an integral cystoscope. This approach may offer a valuable alternative to traditional thoracoscopy in the neonatal period.

Efficient X-ray luminescence imaging with ultrastable and eco-friendly copper(I)-iodide cluster microcubes.

The advancement of contemporary X-ray imaging heavily depends on discovering scintillators that possess high sensitivity, robust stability, low toxicity, and a uniform size distribution. Despite significant progress in this field, the discovery of a material that satisfies all of these criteria remains a challenge. In this study, we report the synthesis of monodisperse copper(I)-iodide cluster microcubes as a new class of X-ray scintillators. The as-prepared microcubes exhibit remarkable sensitivity to X-rays and exceptional stability under moisture and X-ray exposure. The uniform size distribution and high scintillation performance of the copper(I)-iodide cluster microcubes make them suitable for the fabrication of large-area, flexible scintillating films for X-ray imaging applications in both static and dynamic settings.

Bioinspired Strategy for Efficient TiO2/Au/CdS Photocatalysts Based On Mesocrystal Superstructures in Biominerals and Charge-Transfer Pathway in Natural Photosynthesis.

Natural photosynthesis involves an efficient charge-transfer pathway through exquisitely arranged photosystems and electron transport intermediates, which separate photogenerated carriers to realize high quantum efficiency. It inspires a rational design construction of artificial photosynthesis systems and the architectures of semiconductors are essential to achieve optimal performance. Of note, biomineralization processes could form various mesocrystals with well-ordered superstructures for unique optical applications. Inspired by both natural photosynthesis and biomineralization, we construct a ternary superstructure-based mesocrystal TiO2 (meso-TiO2)/Au/CdS artificial photosynthesis system by a green photo-assisted method. The well-ordered superstructure of meso-TiO2 and efficient charge-transfer pathway among the three components are crucial for retarding charge recombination. As a result, the meso-TiO2/Au/CdS photocatalyst displays enhanced visible light-driven photocatalytic hydrogen evolution (4.60 mmol h-1 g-1), which is 3.2 times higher than that of commercial TiO2 (P25)/Au/CdS with disordered TiO2 nanocrystal aggregates (1.41 mmol h-1 g-1). This work provides a promising bioinspired design strategy for photocatalysts with an improved solar conversion efficiency.

Emerging Halide Perovskite Ferroelectrics.

Halide perovskites have gained tremendous attention in the past decade owing to their excellent properties in optoelectronics. Recently, a fascinating property, ferroelectricity, has been discovered in halide perovskites and quickly attracted widespread interest. Compared with traditional perovskite oxide ferroelectrics, halide perovskites display natural advantages such as structural softness, low weight, and easy processing, which are highly desirable in applications pursuing miniaturization and flexibility. This review focuses on the current research progress in halide perovskite ferroelectrics, encompassing the emerging materials systems and their potential applications in ferroelectric photovoltaics, self-powered photodetection, and X-ray detection. The main challenges and possible solutions in the future development of halide perovskite ferroelectric materials are also attempted to be pointed out.

Color-Tunable and Stable Copper Iodide Cluster Scintillators for Efficient X-Ray Imaging.

The search for color-tunable, efficient, and robust scintillators plays a vital role in the development of modern X-ray radiography. The radioluminescence tuning of copper iodide cluster scintillators in the entire visible region by bandgap engineering is herein reported. The bandgap engineering benefits from the fact that the conduction band minimum and valence band maximum of copper iodide cluster crystals are contributed by atomic orbitals from the inorganic core and organic ligand components, respectively. In addition to high scintillation performance, the as-prepared crystalline copper iodide cluster solids exhibit remarkable resistance toward both moisture and X-ray irradiation. These features allow copper iodide cluster scintillators to show particular attractiveness for low-dose X-ray radiography with a detection limit of 55 nGy s-1 , a value ≈100 times lower than a standard dosage for X-ray examinations. The results suggest that optimizing both inorganic core and organic ligand for the building blocks of metal halide cluster crystals may provide new opportunities for a new generation of high-performance scintillation materials.

Organic phosphorescent scintillation from copolymers by X-ray irradiation.

Scintillators that exhibit X-ray-excited luminescence have great potential in radiation detection, X-ray imaging, radiotherapy, and non-destructive testing. However, most reported scintillators are limited to inorganic or organic crystal materials, which have some obstacles in repeatability and processability. Here we present a facile strategy to achieve the X-ray-excited organic phosphorescent scintillation from amorphous copolymers through the copolymerization of the bromine-substituted chromophores and acrylic acid. These polymeric scintillators exhibit efficient X-ray responsibility and decent phosphorescent quantum yield up to 51.4% under ambient conditions. The universality of the design principle was further confirmed by a series of copolymers with multi-color radioluminescence ranging from green to orange-red. Moreover, we demonstrated their potential application in X-ray radiography. This finding not only outlines a feasible principle to develop X-ray responsive phosphorescent polymers, but also expands the potential applications of polymer materials with phosphorescence features.

Arabidopsis ROOT ELONGATION RECEPTOR KINASES negatively regulate root growth putatively via altering cell wall remodeling gene expression.

Receptor-like kinases (RLKs) play key roles in regulating various physiological aspects in plant growth and development. In Arabidopsis thaliana, there are at least 223 leucine-rich repeat (LRR) RLKs. The functions of the majority of RLKs in the LRR XI subfamily were previously revealed. Only three RLKs were not characterized. Here we report that two independent triple mutants of these RLKs, named ROOT ELONGATION RECEPTOR KINASES (REKs), exhibit increased cell numbers in the root apical meristem and enhanced cell size in the elongation and maturation zones. The promoter activities of a number of Quiescent Center marker genes are significantly up-regulated in the triple mutant. However, the promoter activities of several marker genes known to control root stem cell niche activities are not altered. RNA-seq analysis revealed that a number of cell wall remodeling genes are significantly up-regulated in the triple mutant. Our results suggest that these REKs play key roles in regulating root development likely via negatively regulating the expression of a number of key cell wall remodeling genes.

Efficient sampling of high-dimensional free energy landscapes using adaptive reinforced dynamics.

Enhanced sampling methods such as metadynamics and umbrella sampling have become essential tools for exploring the configuration space of molecules and materials. At the same time, they have long faced a number of issues such as the inefficiency when dealing with a large number of collective variables (CVs) or systems with high free energy barriers. Here we show that, with clustering and adaptive tuning techniques, the reinforced dynamics (RiD) scheme can be used to efficiently explore the configuration space and free energy landscapes with a large number of CVs or systems with high free energy barriers. We illustrate this by studying various representative and challenging examples. First we demonstrate the efficiency of adaptive RiD compared with other methods and construct the nine-dimensional (9D) free energy landscape of a peptoid trimer, which has energy barriers of more than 8 kcal mol-1. We then study the folding of the protein chignolin using 18 CVs. In this case, both the folding and unfolding rates are observed to be 4.30 µs-1. Finally, we propose a protein structure refinement protocol based on RiD. This protocol allows us to efficiently employ more than 100 CVs for exploring the landscape of protein structures and it gives rise to an overall improvement of 14.6 units over the initial global distance test-high accuracy (GDT-HA) score.

Overcoming thermal quenching in upconversion nanoparticles.

Thermal quenching that is characterized by loss of light emission with increasing temperature is widely observed in luminescent materials including upconversion nanoparticles, causing problems in technological applications such as lighting, displays, and imaging. Because upconversion processes involve extensive intra-particle energy transfer that is temperature dependent, methods have been established to fight against thermal quenching in upconversion nanoparticles by engineering the energy transfer routes. In this minireview, we discuss the origin of thermal quenching and the role of energy transfer in thermal quenching. Accordingly, recent efforts in overcoming thermal quenching of upconversion are summarized.

DeepTorrent: a deep learning-based approach for predicting DNA N4-methylcytosine sites.

DNA N4-methylcytosine (4mC) is an important epigenetic modification that plays a vital role in regulating DNA replication and expression. However, it is challenging to detect 4mC sites through experimental methods, which are time-consuming and costly. Thus, computational tools that can identify 4mC sites would be very useful for understanding the mechanism of this important type of DNA modification. Several machine learning-based 4mC predictors have been proposed in the past 3 years, although their performance is unsatisfactory. Deep learning is a promising technique for the development of more accurate 4mC site predictions. In this work, we propose a deep learning-based approach, called DeepTorrent, for improved prediction of 4mC sites from DNA sequences. It combines four different feature encoding schemes to encode raw DNA sequences and employs multi-layer convolutional neural networks with an inception module integrated with bidirectional long short-term memory to effectively learn the higher-order feature representations. Dimension reduction and concatenated feature maps from the filters of different sizes are then applied to the inception module. In addition, an attention mechanism and transfer learning techniques are also employed to train the robust predictor. Extensive benchmarking experiments demonstrate that DeepTorrent significantly improves the performance of 4mC site prediction compared with several state-of-the-art methods.

DeepCleave: a deep learning predictor for caspase and matrix metalloprotease substrates and cleavage sites.

MOTIVATION: Proteases are enzymes that cleave target substrate proteins by catalyzing the hydrolysis of peptide bonds between specific amino acids. While the functional proteolysis regulated by proteases plays a central role in the 'life and death' cellular processes, many of the corresponding substrates and their cleavage sites were not found yet. Availability of accurate predictors of the substrates and cleavage sites would facilitate understanding of proteases' functions and physiological roles. Deep learning is a promising approach for the development of accurate predictors of substrate cleavage events. RESULTS: We propose DeepCleave, the first deep learning-based predictor of protease-specific substrates and cleavage sites. DeepCleave uses protein substrate sequence data as input and employs convolutional neural networks with transfer learning to train accurate predictive models. High predictive performance of our models stems from the use of high-quality cleavage site features extracted from the substrate sequences through the deep learning process, and the application of transfer learning, multiple kernels and attention layer in the design of the deep network. Empirical tests against several related state-of-the-art methods demonstrate that DeepCleave outperforms these methods in predicting caspase and matrix metalloprotease substrate-cleavage sites. AVAILABILITY AND IMPLEMENTATION: The DeepCleave webserver and source code are freely available at http://deepcleave.erc.monash.edu/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hydrogenated ZnIn2S4 microspheres: boosting photocatalytic hydrogen evolution by sulfur vacancy engineering and mechanism insight.

In some oxide photocatalysts, changing their surface structure rather than crystal structure by introducing some defects (such as oxygen vacancies) has been proven to be effective in enhancing the separation efficiency of photogenerated carriers and thus photocatalytic activity. To the best of our knowledge, however, such a surface defect engineering strategy for sulfide photocatalysts has rarely been verified. The present work shows the first case of employing pressure hydrogenation to prepare hydrogenated ZnIn2S4 (H-ZIS) microspheres with surface-deficient porous structures, which are favorable for furnishing sufficient surface sulfur vacancies to realize excellent photocatalytic hydrogen evolution reactions. The hydrogen evolution rate (HER) of H-ZIS is as high as 1.9 mmol h-1 g-1 (nearly 8.6 times that of the pristine ZIS sample), which rivals or exceeds those of previously-reported ZIS-based photocatalysts under visible light irradiation. Meanwhile, the inherent correlation between surface sulfur vacancies and photocatalytic activities of H-ZIS is also explored. Thus, this work demonstrates the feasibility of enhancing the hydrogen evolution capability of sulfide photocatalysts by the formation of sulfur vacancies through a pressure hydrogenation process.

Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning.

OBJECTIVE: To observe whether metformin (MET) plays a protective role in acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats by activating the AMPK/NF-κB signaling pathway. METHODS: PQ exposure was used to construct a rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury, and MET intervention was performed. Rat lung tissue samples were collected to evaluate pathological changes in rat lung tissue, the oxidation index, and inflammatory factors; cell viability was detected by CCK-8 assays, and the protein expression levels of phospho-AMPK and phospho-NF-κBp65 in rat lung tissue and RLE-6TN cells were observed by Western blotting. RESULTS: Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 ± 0.31 vs. 5.45 ± 0.40, P < 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 ± 0.19 vs. 3.08 ± 0.15, P < 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 ± 5.22 vs. 45.23 ± 6.58, 30.40 ± 2.84 vs. 21.00 ± 3.20; all P < 0.001) in lung tissue homogenate, (4) reduced levels of IL-1ß, IL-6, and TNF-α in lung tissue homogenates (pg/mL: 47.87 ± 5.06 vs. 66.77 ± 6.55; 93.03 ± 7.41 vs. 107.39 ± 9.81; 75.73 ± 6.08 vs. 89.12 ± 8.94; all P < 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 ± 0.09, 0.76 ± 0.06, and 0.58 ± 0.03 vs. 0.50 ± 0.05; all P < 0.05), (6) decreased protein levels of phospho-NF-κBp65 in lung homogenates and RLE-6TN cells (p-NF-κB/NF-κB: 0.47 ± 0.09 vs. 0.81 ± 0.13; 0.26 ± 0.07 vs. 0.79 ± 0.13; all P < 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 ± 0.05 vs. 0.36 ± 0.12; 0.93 ± 0.03 vs. 0.56 ± 0.15; all P < 0.01). After the addition of the AMPK inhibitor Compound C (Com C), the protein expression levels of phospho-AMPK and phospho-NF-κBp65 returned to baseline. CONCLUSION: MET can effectively alleviate ALI induced by paraquat poisoning and increase the viability of cells exposed to paraquat. The mechanism may be related to the activation of the AMPK/NF-κB pathway, downregulation of inflammatory mediators such as IL-6 and TNF-α, and upregulation of the SOD and GSH-Px oxidation index, and these effects can be inhibited by the AMPK inhibitor Com C.

BES1 is activated by EMS1-TPD1-SERK1/2-mediated signaling to control tapetum development in Arabidopsis thaliana.

BES1 and BZR1 were originally identified as two key transcription factors specifically regulating brassinosteroid (BR)-mediated gene expression. They belong to a family consisting of six members, BES1, BZR1, BEH1, BEH2, BEH3, and BEH4. bes1 and bzr1 single mutants do not exhibit any characteristic BR phenotypes, suggesting functional redundancy of these proteins. Here, by generating higher order mutants, we show that a quintuple mutant is male sterile due to defects in tapetum and microsporocyte development in anthers. Our genetic and biochemical analyses demonstrate that BES1 family members also act as downstream transcription factors in the EMS1-TPD1-SERK1/2 pathway. Ectopic expression of both TPD1 and EMS1 in bri1-116, a BR receptor null mutant, leads to the accumulation of non-phosphorylated, active BES1, similar to activation of BES1 by BRI1-BR-BAK1 signaling. These data suggest that two distinctive receptor-like kinase-mediated signaling pathways share BES1 family members as downstream transcription factors to regulate different aspects of plant development.

[Effects between chest-compression-only cardiopulmonary resuscitation and standard cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: a Meta-analysis].

OBJECTIVE: To comprehensively evaluate and compare the resuscitation efficacy of chest-compression-only cardiopulmonary resuscitation (CCPR) and standard cardiopulmonary resuscitation (SCPR) for patients with out-of-hospital cardiac arrest (OHCA). METHODS: Databases such as PubMed, Embase, Ovid, Cochrane Library, Wanfang, CNKI, VIP, CBM were searched from the date of their foundation to March 2nd 2018, and the studies on the difference of effects between CCPR and SCPR for patients with OHCA were retrieved. The outcomes included the return of spontaneous circulation (ROSC) rate, survival to hospital discharge, neurological function completion rate. Two reviewers independently screened the literature meeting the inclusion criteria, independently collected information and evaluated the literature quality. Meta-analysis was conducted using RevMan 5.3 software, and sensitivity analysis was conducted by selecting model analysis method and removing single research method. Funnel plot was used to evaluate publication bias. RESULTS: A total of 10 cohort studies were included, including 174 163 patients with OHCA, of which 95 157 undergone CCPR and 79 006 undergone SCPR. The scores of the Newcastle-Ottawa scale (NOS) were 8-9, indicating that the quality of the literatures included was high. It was shown by the Meta-analysis that CCPR had the higher rate of survival to hospital discharge [relative risk (RR) = 1.04, 95% confidence interval (95%CI) = 1.00-1.08, P = 0.04] and neurological function completion (RR = 1.11, 95%CI = 1.06-1.17, P < 0.000 1) than SCPR, but there was no significant difference in ROSC rate between the two groups (RR = 1.01, 95%CI = 0.98-1.04, P = 0.52). In the subgroup, there was no statistical significance between CCPR and SCPR in the rate of survival to hospital discharge in cardiac OHCA patients (RR = 1.13, 95%CI = 0.82-1.57, P = 0.45). However, in non-cardiac OHCA group, SCPR showed more benefits than CCPR in improving the rate of survival to hospital discharge (RR = 0.88, 95%CI = 0.80-0.96, P = 0.004). The above analysis results were consistent in the fixed effect model and random effect model, indicating that the results were reliable and stable. It was shown by the funnel plot that most of the studies were left-right inverted funnel type, indicating a low publication bias. However, the bias could not be completely excluded due to the small number of included literatures. CONCLUSIONS: For patients without OHCA etiological classification, CCPR was not less than SCPR in improving ROSC rate, discharge survival rate and good neurological function, and CCPR was more advantageous in learning and the willingness of bystanders to implement. However, when non-cardiogenic OHCA could be identified, SCPR should be recommended when conditions permit.