How to achieve high-quality development of SRDI enterprises-A study of the TOE framework-based configuration.

The high-quality development of SRDI enterprises is crucial for China to overcome critical technological bottlenecks and thereby achieve technological independence and strength. However, the factors driving the high-quality development of SRDI enterprises are not isolated elements, but rather a complex system of interconnected antecedents. This study employs the TOE framework and fuzzy set Qualitative Comparative Analysis (fsQCA) with 141 Chinese SRDI "little giant" listed companies as samples to explore how various factors contribute to their high-quality development. The findings indicate: (1) No single factor is necessary for SRDI enterprises' high-quality development. (2) It is the synergy of multiple factors, in various combinations, that drives their high-quality development. (3) Technological innovation plays a key role in these pathways; SRDI enterprises should leverage their resources and capabilities for a synergistic technology-organization-environment match, selecting the most suitable development path. The results of this study not only enrich our understanding of the factors influencing SRDI enterprises' high-quality development but also offer insights for both the enterprises and government policy-making.

Ultrahigh Bifunctional Photocatalytic CO2 Reduction and H2 Evolution by Synergistic Interaction of Heteroatomic Pt-Ru Dimerization Sites.

Diatomic-site catalysts (DASCs) inherit the excellent performance of single-atom catalysts (SACs) by utilizing two adjacent atomic metal species to achieve functional complementarity and synergistic effects that improve the carbon dioxide reduction reaction (CO2RR) and H2 evolution reaction (HER) kinetics. Herein, we report a method to further improve the catalytic efficiency of Pt by using Pt and Ru single atoms randomly anchored on a g-C3N4 surface, yielding partial Pt-Ru dimers. The synthesized catalyst exhibits extraordinary photocatalytic activity and stability in both the CO2RR and HER processes. In-depth experimentation, the pH-dependent chemical exchange saturation transfer (CEST) imaging nuclear magnetic resonance (NMR) method, and theoretical analyses reveal that the excellent performance is attributed to orbital coupling between the Pt atoms and the neighboring Ru atoms (mainly dxy and dxz), which decreases the orbital energy levels and weakens the bond strength with intermediates, resulting in improved CO2RR and HER performance. This study successfully applies the pH-dependent CEST imaging NMR method to catalytic reactions, and CO2 adsorption is directly observed using CEST 2D imaging maps. This work presents significant potential for a variety of catalytic reaction applications by systematically designing bimetallic dimers with higher activity and stability.

19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor.

For the A2A adenosine receptor (A2AAR), a class A G-protein-coupled receptor (GPCR), reconstituted in n-dodecyl-ß-D-maltoside (DDM)/|||||cholesteryl hemisuccinate (CHS) mixed micelles, previous 19F-NMR studies revealed the presence of multiple simultaneously populated conformational states. Here, we study the influence of a different detergent, lauryl maltose neopentyl glycol (LMNG) in mixed micelles with CHS, and of lipid bilayer nanodiscs on these conformational equilibria. The populations of locally different substates are pronouncedly different in DDM/|||||CHS and LMNG/|||||CHS micelles, whereas the A2AAR conformational manifold in LMNG/|||||CHS micelles is closely similar to that in the lipid bilayer nanodiscs. Considering that nanodiscs represent a closer match of the natural lipid bilayer membrane, these observations support that LMNG/|||||CHS micelles are a good choice for reconstitution trials of class A GPCRs for NMR studies in solution.

Inhibitory to non-inhibitory evolution of the ζ subunit of the F1FO-ATPase of Paracoccus denitrificans and α-proteobacteria as related to mitochondrial endosymbiosis.

Introduction: The ζ subunit is a potent inhibitor of the F1FO-ATPase of Paracoccus denitrificans (PdF1FO-ATPase) and related α-proteobacteria different from the other two canonical inhibitors of bacterial (ε) and mitochondrial (IF1) F1FO-ATPases. ζ mimics mitochondrial IF1 in its inhibitory N-terminus, blocking the PdF1FO-ATPase activity as a unidirectional pawl-ratchet and allowing the PdF1FO-ATP synthase turnover. ζ is essential for the respiratory growth of P. denitrificans, as we showed by a Δζ knockout. Given the vital role of ζ in the physiology of P. denitrificans, here, we assessed the evolution of ζ across the α-proteobacteria class. Methods: Through bioinformatic, biochemical, molecular biology, functional, and structural analyses of several ζ subunits, we confirmed the conservation of the inhibitory N-terminus of ζ and its divergence toward its C-terminus. We reconstituted homologously or heterologously the recombinant ζ subunits from several α-proteobacteria into the respective F-ATPases, including free-living photosynthetic, facultative symbiont, and intracellular facultative or obligate parasitic α-proteobacteria. Results and discussion: The results show that ζ evolved, preserving its inhibitory function in free-living α-proteobacteria exposed to broad environmental changes that could compromise the cellular ATP pools. However, the ζ inhibitory function was diminished or lost in some symbiotic α-proteobacteria where ζ is non-essential given the possible exchange of nutrients and ATP from hosts. Accordingly, the ζ gene is absent in some strictly parasitic pathogenic Rickettsiales, which may obtain ATP from the parasitized hosts. We also resolved the NMR structure of the ζ subunit of Sinorhizobium meliloti (Sm-ζ) and compared it with its structure modeled in AlphaFold. We found a transition from a compact ordered non-inhibitory conformation into an extended α-helical inhibitory N-terminus conformation, thus explaining why the Sm-ζ cannot exert homologous inhibition. However, it is still able to inhibit the PdF1FO-ATPase heterologously. Together with the loss of the inhibitory function of α-proteobacterial ε, the data confirm that the primary inhibitory function of the α-proteobacterial F1FO-ATPase was transferred from ε to ζ and that ζ, ε, and IF1 evolved by convergent evolution. Some key evolutionary implications on the endosymbiotic origin of mitochondria, as most likely derived from α-proteobacteria, are also discussed.

Two-Dimensional NMR Spectroscopy of the G Protein-Coupled Receptor A2AAR in Lipid Nanodiscs.

Eight hundred and twenty-six human G protein-coupled receptors (GPCRs) mediate the actions of two-thirds of the human hormones and neurotransmitters and over one-third of clinically used drugs. Studying the structure and dynamics of human GPCRs in lipid bilayer environments resembling the native cell membrane milieu is of great interest as a basis for understanding structure-function relationships and thus benefits continued drug development. Here, we incorporate the human A2A adenosine receptor (A2AAR) into lipid nanodiscs, which represent a detergent-free environment for structural studies using nuclear magnetic resonance (NMR) in solution. The [15N,1H]-TROSY correlation spectra confirmed that the complex of [u-15N, ~70% 2H]-A2AAR with an inverse agonist adopts its global fold in lipid nanodiscs in solution at physiological temperature. The global assessment led to two observations of practical interest. First, A2AAR in nanodiscs can be stored for at least one month at 4 °C in an aqueous solvent. Second, LMNG/CHS micelles are a very close mimic of the environment of A2AAR in nanodiscs. The NMR signal of five individually assigned tryptophan indole 15N-1H moieties located in different regions of the receptor structure further enabled a detailed assessment of the impact of nanodiscs and LMNG/CHS micelles on the local structure and dynamics of A2AAR. As expected, the largest effects were observed near the lipid-water interface along the intra- and extracellular surfaces, indicating possible roles of tryptophan side chains in stabilizing GPCRs in lipid bilayer membranes.

The Application of Radiolabeled Targeted Molecular Probes for the Diagnosis and Treatment of Prostate Cancer.

Radiopharmaceuticals targeting prostate-specific membrane antigens (PSMA) are essential for the diagnosis, evaluation, and treatment of prostate cancer (PCa), particularly metastatic castration-resistant PCa, for which conventional treatment is ineffective. These molecular probes include [68Ga]PSMA, [18F]PSMA, [Al18F]PSMA, [99mTc]PSMA, and [89Zr]PSMA, which are widely used for diagnosis, and [177Lu]PSMA and [225Ac]PSMA, which are used for treatment. There are also new types of radiopharmaceuticals. Due to the differentiation and heterogeneity of tumor cells, a subtype of PCa with an extremely poor prognosis, referred to as neuroendocrine prostate cancer (NEPC), has emerged, and its diagnosis and treatment present great challenges. To improve the detection rate of NEPC and prolong patient survival, many researchers have investigated the use of relevant radiopharmaceuticals as targeted molecular probes for the detection and treatment of NEPC lesions, including DOTA-TOC and DOTA-TATE for somatostatin receptors, 4A06 for CUB domain-containing protein 1, and FDG. This review focused on the specific molecular targets and various radionuclides that have been developed for PCa in recent years, including those mentioned above and several others, and aimed to provide valuable up-to-date information and research ideas for future studies.

Is a classical incision the only way to perform a near-term conjoined twins' cesarean section? Thoracopagus conjoined twin delivery by a low-segment transverse incision.

Conjoined twin pregnancies are rare, usually occurring in cases of monochorionic monoamniotic twin pregnancies. The most common type of conjoined twins, thoracopagus (42%), is difficult to deliver via a low-segment transverse incision hysterotomy after 35 weeks of gestation. Therefore, conjoined twin cesarean deliveries are typically performed using the classical incision method. However, this often leads to an increased risk of postoperative maternal morbidity and uterine rupture during a subsequent pregnancy. Because of the low survival rate of conjoined twins, subsequent pregnancies are often desired. Hence, minimizing trauma to the uterus is a primary concern. A technique for delivering conjoined twins at 35 weeks of gestation by cesarean delivery with a low-segment transverse incision hysterotomy is proposed here. A video is included to explain and demonstrate these procedures. This method can minimize uterine trauma and maximize the chances of a successful subsequent pregnancy.

Chromosome-level genome assembly and population genomics of Mongolian racerunner (Eremias argus) provide insights into high-altitude adaptation in lizards.

BACKGROUND: Although the extreme environmental adaptation of organisms is a hot topic in evolutionary biology, genetic adaptation to high-altitude environment remains poorly characterized in ectothermic animals. Squamates are among the most diverse terrestrial vertebrates, with tremendous ecological plasticity and karyotype diversity, and are a unique model system to investigate the genetic footprints of adaptation. RESULTS: We report the first chromosome-level assembly of the Mongolian racerunner (Eremias argus) and our comparative genomics analyses found that multiple chromosome fissions/fusions events are unique to lizards. We further sequenced the genomes of 61 Mongolian racerunner individuals that were collected from altitudes ranging from ~ 80 to ~ 2600 m above sea level (m.a.s.l.). Population genomic analyses revealed many novel genomic regions under strong selective sweeps in populations endemic to high altitudes. Genes embedded in those genomic regions are mainly associated with energy metabolism and DNA damage repair pathways. Moreover, we identified and validated two substitutions of PHF14 that may enhance the lizards' tolerance to hypoxia at high altitudes. CONCLUSIONS: Our study reveals the molecular mechanism of high-altitude adaptation in ectothermic animal using lizard as a research subject and provides a high-quality lizard genomic resource for future research.

Whole genome analyses reveal novel genes associated with chicken adaptation to tropical and frigid environments.

INTRODUCTION: Investigating the genetic footprints of historical temperature selection can get insights to the local adaptation and feasible influences of climate change on long-term population dynamics. OBJECT: Chicken is a significative species to study genetic adaptation on account of its similar domestication track related to human activity with the most diversified varieties. Yet, few studies have demonstrated the genetic signatures of its adaptation to naturally tropical and frigid environments. METHOD: Here, we generated whole genome resequencing of 119 domesticated chickens in China including the following breeds which are in order of breeding environmental temperature from more tropical to more frigid: Wenchang chicken (WCC), green-shell chicken (GSC), Tibetan chicken (TBC), and Lindian chicken (LDC). RESULTS: Our results showed WCC branched off earlier than LDC with an evident genetic admixture between WCC and LDC, suggesting their closer genetic relationship. Further comparative genomic analyses solute carrier family 33 member 1 (SLC33A1) and thyroid stimulating hormone receptor (TSHR) genes exhibited stronger signatures for positive selection in the genome of the more tropical WCC. Furthermore, genotype data from about 3,000 African local ecotypes confirmed that allele frequencies of single nucleotide polymorphisms (SNPs) in these 2 genes appeared strongly associated with tropical environment adaptation. In addition, the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) gene exhibited a strong signature for positive selection in the LDC genome, and SNPs with marked allele frequency differences indicated a significant relationship with frigid environment adaptation. CONCLUSION: Our findings partially clarify how selection footprints from environmental temperature stress can lead to advantageous genomic adaptions to tropical and frigid environments in poultry and provide a valuable resource for selective breeding of chickens.

Different Intermolecular Interactions Drive Nonpathogenic Liquid-Liquid Phase Separation and Potentially Pathogenic Fibril Formation by TDP-43.

The liquid-liquid phase separation (LLPS) of proteins has been found ubiquitously in eukaryotic cells, and is critical in the control of many biological processes by forming a temporary condensed phase with different bimolecular components. TDP-43 is recruited to stress granules in cells and is the main component of TDP-43 granules and proteinaceous amyloid inclusions in patients with amyotrophic lateral sclerosis (ALS). TDP-43 low complexity domain (LCD) is able to de-mix in solution, forming the protein condensed droplets, and amyloid aggregates would form from the droplets after incubation. The molecular interactions regulating TDP-43 LCD LLPS were investigated at the protein fusion equilibrium stage, when the droplets stopped growing after incubation. We found the molecules in the droplet were still liquid-like, but with enhanced intermolecular helix-helix interactions. The protein would only start to aggregate after a lag time and aggregate slower than at the condition when the protein does not phase separately into the droplets, or the molecules have a reduced intermolecular helix-helix interaction. In the protein condensed droplets, a structural transition intermediate toward protein aggregation was discovered involving a decrease in the intermolecular helix-helix interaction and a reduction in the helicity. Our results therefore indicate that different intermolecular interactions drive LLPS and fibril formation. The discovery that TDP-43 LCD aggregation was faster through the pathway without the first protein phase separation supports that LLPS and the intermolecular helical interaction could help maintain the stability of TDP-43 LCD.

Squamous cell carcinoma in mature cystic teratoma of the ovary induced by human papillomavirus 16 infection: A case report and literature review.

RATIONALE: Mature cystic teratoma is the most common ovarian germ cell tumor. The malignant transformation of ovarian mature cystic teratoma (MCT) is very rare, but the prognosis is poor. We present a case of ovarian mature cystic teratoma with human papillomavirus infection and malignant transformation into ovarian squamous cell carcinoma (SCC). The occurrence of this case may prove that high-risk human papillomavirus infection is a pathogenic factor inducing malignant transformation of mature cystic teratoma to SCC. PATIENT CONCERNS: A 38-year-old woman with a solid cystic mass of 8 cm on the right ovary, and human papillomavirus (HPV) test of her cervix showed HPV-16 infection. DIAGNOSIS: The transvaginal ultrasound was performed, and there was a cystic solid mass of 5.9 × 4.5 × 5.5 cm in the right adnexal area with unclear cystic fluid and rich blood flow signals in the capsule wall. HPV test of cervix showed HPV-16 infection. Diagnostic suspicion: cystic teratoma. INTERVENTION: The patient signed an laparoendoscopic surgery was performed to remove the right ovarian mass. Intraoperative pathology consultation revealed the malignant transformation of mature teratoma of the right ovary and the formation of squamous or adeno-SCC. We performed laparoscopic comprehensive surgical staging (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, pelvic and para-aortic lymph node dissection) were made. OUTCOMES: The operation was successful and the postoperative recovery was smooth, was discharged 7 days after operation. Now the patient is recovering well and is continuing chemotherapy as planned. CONCLUSION: HR-HPV infection might be a causal factor for inducing malignant transformation of ovarian MCT to SCC, and the Jumping metastasis of lymph nodes may be the characteristic of SCC-MCT, but further verification is still needed.

GPCR structural characterization by NMR spectroscopy in solution.

In the human proteome, 826 G-protein-coupled receptors (GPCRs) interact with extracellular stimuli to initiate cascades of intracellular signaling. Determining conformational dynamics and intermolecular interactions are key to understand GPCR function as a basis for drug design. X-ray crystallography and cryo-electron microscopy (cryo-EM) contribute molecular architectures of GPCRs and GPCR-signaling complexes. NMR spectroscopy is complementary by providing information on the dynamics of GPCR structures at physiological temperature. In this review, several NMR approaches in use to probe GPCR dynamics and intermolecular interactions are discussed. The topics include uniform stable-isotope labeling, amino acid residue-selective stable-isotope labeling, site-specific labeling by genetic engineering, the introduction of 19F-NMR probes, and the use of paramagnetic nitroxide spin labels. The unique information provided by NMR spectroscopy contributes to our understanding of GPCR biology and thus adds to the foundations for rational drug design.

tert-Butyl Hydroperoxide Promoted the Reaction of Quinazoline-3-oxides with Primary Amines Affording Quinazolin-4(3H)-ones.

An efficient and facile approach for the synthesis of quinazolin-4(3H)-ones via the reaction of quinazoline-3-oxides with primary amines is described. This approach is demonstrated to be applicable for a broad range of substrates and proceeds efficiently under metal-free and mild reaction conditions employing easily available tert-butyl hydroperoxide as the oxidant. Remarkably, 3-(2-(1H-indol-3-yl) ethyl)quinazolin-4(3H)-one 3w, which was conveniently obtained by this process in 70% yield, was an excellent precursor for the synthesis of bioactive evodiamine and rutaempine.

G Protein-coupled Receptor (GPCR) Reconstitution and Labeling for Solution Nuclear Magnetic Resonance (NMR) Studies of the Structural Basis of Transmembrane Signaling.

G protein-coupled receptors (GPCRs) are a large membrane protein family found in higher organisms, including the human body. GPCRs mediate cellular responses to diverse extracellular stimuli and thus control key physiological functions, which makes them important targets for drug design. Signaling by GPCRs is related to the structure and dynamics of these proteins, which are modulated by extrinsic ligands as well as by intracellular binding partners such as G proteins and arrestins. Here, we review some basics of using nuclear magnetic resonance (NMR) spectroscopy in solution for the characterization of GPCR conformations and intermolecular interactions that relate to transmembrane signaling.

GPCR large-amplitude dynamics by 19F-NMR of aprepitant bound to the neurokinin 1 receptor.

Comparisons of G protein-coupled receptor (GPCR) complexes with agonists and antagonists based on X-ray crystallography and cryo-electron microscopy structure determinations show differences in the width of the orthosteric ligand binding groove over the range from 0.3 to 2.9 Å. Here, we show that there are transient structure fluctuations with amplitudes up to at least 6 Å. The experiments were performed with the neurokinin 1 receptor (NK1R), a GPCR of class A that is involved in inflammation, pain, and cancer. We used 19F-NMR observation of aprepitant, which is an approved drug that targets NK1R for the treatment of chemotherapy-induced nausea and vomiting. Aprepitant includes a bis-trifluoromethyl-phenyl ring attached with a single bond to the core of the molecule; 19F-NMR revealed 180° flipping motions of this ring about this bond. In the picture emerging from the 19F-NMR data, the GPCR transmembrane helices undergo large-scale floating motions in the lipid bilayer. The functional implication is of extensive promiscuity of initial ligand binding, primarily determined by size and shape of the ligand, with subsequent selection by unique interactions between atom groups of the ligand and the GPCR within the binding groove. This second step ensures the wide range of different efficacies documented for GPCR-targeting drugs. The NK1R data also provide a rationale for the observation that diffracting GPCR crystals are obtained for complexes with only very few of the ligands from libraries of approved drugs and lead compounds that bind to the receptors.

Copper-Catalyzed Oxidative Coupling of Quinazoline-3-Oxides: Synthesis of O-Quinazolinic Carbamates.

Organic carbamates represent a kind of privileged structures in both organic chemistry and industry. Despite the fact that the synthesis of alcohol-based carbamates has been well studied, an efficient access to hydroxamic acid-based carbamates is less explored due to the nucleophilicity of both O and N atoms in hydroxamic acids. Herein, we report a copper-catalyzed oxidative coupling of quinazoline-3-oxides and formamides for the synthesis of O-quinazolinic carbamates. This protocol is featured with practicability, simple starting materials, and operational simplicity.

Application of the defect management improvement mode under Joint Commission International standard to improve the instrument cleaning and disinfection effect and management quality in the central sterile supply department: a randomized trial.

Background: Professional, standardized, and scientific management of the disinfection supply room is the prerequisite to ensure medical quality and improve the comprehensive strength of the hospital. This study aimed to evaluate the application of the defect management improvement mode of the Joint Commission International (JCI) standard in improving the cleaning and disinfection effect as well as the management quality of instruments in the central sterile supply department (CSSD). Methods: From January 2020 to December 2020, 32 medical staff in the hospital CSSD were divided into control and observation groups according to the random number table method, with 16 staff members in each group. The control group adopted the standardized management mode and the observation group adopted the defect management improvement mode based on the JCI standard. During the management period, we compared the disinfection effect and incidence of adverse events of the instruments and articles in the CSSD of the two groups, and evaluated the work and satisfaction of both groups of subjects. Linear correlation analysis and multiple linear regression analysis were used to determine the influencing factors of satisfaction. Results: During the standardized management, the instruments and articles were used 611 times in the control group and 602 times in the observation group. The cleaning qualified rate, infection awareness rate, standard implementation rate, hand hygiene implementation rate, theoretical knowledge score, and practical operation ability of the observation group were significantly higher than those of the control group (P<0.05). The incidence of adverse events in the observation group was significantly lower compared to the control group (P<0.05), and the satisfaction scores of the observation group were significantly higher than those of the control group (P<0.05). The total satisfaction score is independently related to the training method, educational background, and professional title. Conclusions: Adopting the defect management improvement mode under the JCI standard for CSSD is conducive to improving the cleaning effect of instruments, enhancing the work situation and job satisfaction of medical staff, and reducing the incidence of adverse events. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100053068.

Management of pregnancy with diffuse cutaneous systemic sclerosis: a case report and literature review.

Diffuse cutaneous systemic sclerosis may occur in women of childbearing age. Pregnancies in this population are associated with a markedly increased risk of adverse obstetric and maternal outcomes even before the onset of symptoms related to sclerosis. We report a case involving the management and outcome of pregnancy in a 30-year-old woman with diffuse cutaneous systemic sclerosis. The course of her pregnancy was good and was assisted by a group consultation including obstetricians and rheumatologists. Vaginal delivery was the patient's preferred choice because she had irregular skin tightness in her lower abdominal skin. She underwent induction of labor and combined spinal-epidural analgesia, and successfully delivered. Importantly, these pregnancies need to be planned, where possible, to allow the opportunity to counsel women and their partners in advance and to decrease any risks. These pregnancies should be considered high risk, and they require close antenatal monitoring and good supervision from an expert multidisciplinary team experienced in high-risk pregnancies. The management of delivery for patients with cutaneous systemic sclerosis is challenging, and vaginal delivery with labor analgesia is an alternative option to cesarean section.