Search

Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Irhas been well-designed as a ferroptosis inducer. NA-Ircould selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP–AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

This article investigates the dynamic-memory event-triggered (DMET)-based double asynchronous dissipative control issue for Takagi–Sugeno fuzzy semi-Markov jump systems (T-S FSMJSs) under redundant channel strategy. To mitigate the network burden and improve the system control performance, a new DMET mechanism is skillfully developed by adopting weighted past released packets of measured output and dynamically adjusted thresholds. Due to the impact of network environment, a novel framework of DMET-based controller scheme is constructed by considering the premise variable asynchronous and mode asynchronous phenomena between the plant and controller simultaneously. The imperfect premise matching and hidden semi-Markov model approaches are employed to resolve two types of mismatches. The redundant channel communication strategy with quantization measurement is used to improve the nonfragility of signal transmission. In terms of the stochastic theory and fuzzy model technique, some criteria are forwarded to ensure the stochastic stability and strict dissipative performance for closed-loop T-S FSMJSs. By the matrix decoupling method, the control scheme is established. Lastly, a single-link robot arm system example is presented to certify the effectiveness of the developed result.

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus Sclerotinia sclerotiorumhas led to serious losses in the yields of oilseed rape and other crops every year. Here, we designed and synthesized a series of carboxamide derivatives containing a diphenyl ether skeleton by adopting the scaffold splicing strategy. From the results of the mycelium growth inhibition experiment, inhibition rates of compounds 4jand 4ishowed more than 80% to control S. sclerotiorumat a dose of 50 μg/mL, which is close to that of the positive control (flubeneteram, 95%). Then, the results of a structure–activity relationship study showed that the benzyl scaffold was very important for antifungal activity and that introducing a halogen atom on the benzyl ring would improve antifungal activity. Furthermore, the results of an in vitro activity test suggested that these novel compounds can inhibit the activity of succinate dehydrogenase (SDH), and the binding mode of 4jwith SDH was basically similar to that of the flutolanil derivative. Morphological observation of mycelium revealed that compound 4jcould cause a damage on the mycelial morphology and cell structure of S. sclerotiorum, resulting in inhibition of the growth of mycelia. Furthermore, in vivo antifungal activity assessment of 4jdisplayed a good control of S. sclerotiorum(>97%) with a result similar to that of the positive control at a concentration of 200 mg/L. Thus, the diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further development.

We have developed an efficient and green strategy for the synthesis of C2-amino indolin-3-ones and C2-acyloxy indolin-3-ones via KI-catalyzed C(sp3)–H amination and acyloxylation of indolin-3-ones using air as the oxidant. The reaction provides straightforward access to 2-substituted indolin-3-ones by the direct functionalization of indolin-3-ones at the C2 position under mild conditions. Moreover, the conditions enable direct functionalization of a range of complex pharmaceuticals, providing attractive products for medicinal chemistry programs.

Burn wounds require intervention to ensure timely progression to reduce morbidity and mortality. The migrative and proliferative capabilities of keratinocytes are impaired in wounds. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix (ECM), allowing epithelial cells to migrate. As reported, osteopontin can regulate cell migration, cell adhesion, and ECM invasion in endothelial and epithelial cells, and its expression is significantly increased in chronic wounds. Therefore, this study investigates the biological functions of osteopontin and its related mechanisms involved in burn wounds. We established cellular and animal models of burn injury. Levels of osteopontin, RUNX1, MMPs, collagen I, CK19, PCNA, and pathway-associated proteins were measured by RT-qPCR, western blotting, and immunofluorescence staining. Cell viability and migration were examined by CCK-8 and wound scratch assays. Histological changes were analyzed by hematoxylin and eosin staining and Masson’s trichrome staining. For in vitro analysis, osteopontin silencing facilitated the growth and migration of HaCaT cells and promoted ECM degradation in HaCaT cells. Mechanistically, RUNX1 bound to osteopontin promoter, and RUNX1 upregulation attenuated the promoting efficacy of osteopontin silencing on cell growth and migration and ECM degradation. Additionally, RUNX1-activated osteopontin inactivated the MAPK signaling pathway. For in vivo analysis, osteopontin depletion facilitated burn wound healing by promoting reepithelialization and ECM degradation. In conclusion, RUNX1 activates the osteopontin expression at the transcriptional level and osteopontin depletion facilitates the recovery of burn wounds by promoting the migration of keratinocytes and reepithelization and ECM degradation by activating the MAPK pathway.

This article is concerned with the security $\mathcal {H}_{\infty }$ fuzzy control problem for Takagi–Sugeno (T–S) fuzzy semi-Markov switching systems (SMSSs) with event-based strategy and hybrid cyber-attacks. To efficiently use network resources and avoid unnecessary signal transmission, a new mode-dependent dynamic event-triggered mechanism (ETM), whose threshold parameter changes with varying states and modes is developed for each subsystem of fuzzy SMSSs. A more practical network environment subject to deception and denial-of-service (DoS) attacks is considered, and two Bernoulli distributed variables are adopted to characterize the randomly occurring hybrid attacks in a unified framework. By the mode-dependent Lyapunov function, sufficient conditions are attained to assure that the closed-loop system is stochastically stable with an $\mathcal {H}_{\infty }$ attenuation performance. Finally, the validity and superiority of the proposed theoretical approach is demonstrated via its application to the Duffing–Van der Pols oscillator.

High luminance blue Micro‐LEDs were designed and fabricated in 4×4 and 8×8 arrays, with a size of 18 × 36μm. Our results showed that the performance of the LED arrays is comparable to that of a single LED, with smoother data. Testing a certain number of LED arrays under the same current density can better reflect the performance of a single LED device. Additionally, for small current range tests, the lack of precision in the testing equipment can be compensated for by appropriately increasing the number of LEDs.

High luminance blue Micro-LEDs were designed and fabricated in 4×4 and 8×8 arrays, with a size of 18× 36μm. Our results showed that the performance of the LED arrays is comparable to that of a single LED, with smoother data. Testing a certain number of LED arrays under the same current density can better reflect the performance of a single LED device. Additionally, for small current range tests, the lack of precision in the testing equipment can be compensated for by appropriately increasing the number of LEDs.

Background: Improving generic drug development in oncology is a key long-term goal in providing safe, effective, and affordable care to patients with a diagnosis of cancer in the United States. There are multiple drug and non-drug related variables that may influence generic drug development. To illustrate pertinent associations relevant to generic drug competition in oncology, our study assessed variables that have potentially led to difference in generic competition as compared to drug products in other therapeutic areas, i.e., cardiovascular disease in this case. Methods: Using a combination of FDA and publicly available data, we categorized individual drug approvals from 1950 to 2021 with either an oncology or cardiovascular indication. Descriptive statistics highlighted the timeline of approval as stratified by indications. Machine learning methodology was used to assess variables associated with abbreviated new drug application (ANDA) availabilities (i.e., generic drug availabilities). Kaplan–Meier analysis with log-rank test compared the difference in the time to approval of first ANDA among products that were off-patent at the time of analysis. A multivariable Cox proportional hazards model with forward selection was used to identify variables (e.g., regulatory recommendation issued, dosage form) that were associated with ANDA availability among products that were off-patent. Results: 434 separate reference listed drugs (RLDs) with varying strengths were identified, 212 (49%) for oncology and 222 (51%) for cardiovascular indications. Compared with cardiovascular products, a greater proportion of RLDs with an oncology indication were approved after 2000 (61% vs. 34%). Also, a smaller proportion of oncologic products had generics (49% vs. 80%). Machine learning methodology revealed RLD age, patent status, product complexity, sales/prescriptions, and regulatory recommendations as variables that were associated with generic availability. Among products off-patent at the time of analysis, the median time from RLD approval to the first ANDA approval was longer for oncologic products compared to cardiovascular products (15.4 years (95% CI 13.8, 17.9) versus 12.3 years (95% CI 10.7, 13.5), p= 0.008). Cox regression analyses identified the variables of product dosage form and regulatory recommendation of requiring patient enrollment for bioequivalence (BE) establishment as being associated with reduced likelihood of ANDA approval for oncologic drugs. Conclusion: Oncology indications were found to have a longer time from RLD approval to first ANDA approval compared with cardiovascular drugs. Our work has identified variables that may influence time to ANDA availability, with the requirement of patient enrollment for BE assessment as one important opportunity for future stakeholder engagement and regulatory considerations.

Nonlinear Fourier transform (NFT)-based nonlinear frequency division multiplexing (NFDM) system has the potential to overcome the limit of fiber nonlinearity. In the NFDM system, the symbol information is modulated onto the nonlinear spectra, which consist of continuous and discrete spectrum. In theory, the dual-polarization (DP) NFDM system with the continuous and discrete spectrum (full spectrum, FS) modulation has the potential to achieve higher spectral efficiency. However, due to the complexity of the NFT and inverse NFT (INFT) numerical algorithms, the DP-FS modulated NFDM system is rarely reported. For the FS-NFDM system, the existing INFT algorithms either only support q-modulation and present poor performance, or have large discrete spectral error as the continuous spectrum energy increases. In this paper, we propose an INFT algorithm design theory. Based the theory, an accurate DP-INFT algorithm is proposed. The algorithm supports not only q-modulation, but also b-modulation with better performance. Employing the proposed INFT algorithm, we demonstrate, for the first time, a 174.5 Gbit/s FS modulated NFDM transmission system with 1440 km.

The synergetic biological effect of scaffolds with biomimetic properties including the ECM micro-architecture and intestinal macro-mechanical properties on intestinal models in vitroremains unclear. Here, we investigate the profitable role of biomimetic scaffolds on 3D intestinal epithelium models. Gelatin/bacterial cellulose nanofiber composite scaffolds crosslinked by the Maillard reaction are tuned to mimic the chemical component, nanofibrous network, and crypt architecture of intestinal ECM collagen and the stability and mechanical properties of intestinal tissue. In particular, scaffolds with comparable elasticity and viscoelasticity of intestinal tissue possess the highest biocompatibility and best cell proliferation and differentiation ability, which makes the intestinal epithelium models closest to their counterpart intestinal tissues. The constructed duodenal epithelium models and colon epithelium models are utilized to assess the immunobiotics–host interactions, and both of them can sensitively respond to foreign microorganisms, but the secretion levels of cytokines are intestinal cell specific. The results demonstrate that probiotics alleviate the inflammation and cell apoptosis induced by Escherichia coli, indicating that probiotics can protect the intestinal epithelium from damage by inhibiting the adhesion and invasion of E. colito intestinal cells. The designed biomimetic scaffolds can serve as powerful tools to construct in vitrointestinal epithelium models, providing a convenient platform to screen intestinal anti-inflammatory components and even to assess other physiological functions of the intestine.

Bacteria colonizing the gastrointestinal tract generally grow well in biofilms. In recent years, probiotic biofilms have been considered the most promising fourth-generation probiotics. However, the research into the functions of probiotic biofilms is just starting. In this study, Lactobacillus reuteriDSM 17938 biofilms formed on electrospun cellulose acetate nanofibrous scaffolds were contrasted with planktonic cells. Pathogen inhibition analysis of Escherichia coli, Staphylococcus aureus, and Listeria monocytogenessuggested a significant distinction between the planktonic and biofilm groups. In human fecal fermentation, L. reuteriremodeled the microbiota by decreasing the relative abundances of Proteobacteria, Escherichia–Shigella, and Desulfovibrioand increasing the relative abundances of Phascolarctobacterium, Bacteroides, and Lactobacillus. Moreover, L. reuteribiofilms played more positive roles in microbiota modulation and short-chain fatty acid production than planktonic L. reuteri. These findings provide an understanding of the beneficial effects of probiotic biofilms, laying a foundation for the application of probiotic biofilms as a health promoter.

Biofilms are the oldest, most successful, and most widely distributed form of microorganism life on earth, existing even in extreme environments. Presently, probiotics in biofilm phenotype are thought as the most advanced fourth-generation probiotics. However, high-efficiency and large-scale biofilm enrichment in an artificial way is difficult. Here, fibrous membranes as probiotic biofilm-enriching materials are studied. Electrospun cellulose acetate nanofibrous membranes with nano-sized fibers show outstanding superiority over fibrous membranes with micron-sized fibers in Lactobacillus paracaseibiofilm enrichment. The special 3D structure of electrospun nanofibrous membranes makes other facilitating biofilm formation factors insignificant. With a suitable scaffold/culture medium ratio, nearly 100% of L. paracaseicells exist as biofilm phenotype on the membrane from the very beginning, not planktonic state. L. paracaseibiofilms possess a potential for long-term survival and high tolerances toward strong acidic and alkali conditions and antibiotics. RNA sequencing results explain why L. paracaseibiofilms possess high tolerances toward harsh environments as compared to planktonic L. paracasei. Electrospun nanofibrous membranes can serve as powerful biofilm-enriching scaffolds for probiotics and other valuable microbes.

Supplemental Digital Content is Available in the Text.Dual antiplatelet therapy (DAPT) is recommended among patients with established acute coronary syndrome. In this meta-analysis, we sought to compare the clinical outcomes between de-escalation versus unchanged DAPT based on both randomized controlled trials (RCTs) and observational studies. The primary outcomes were major adverse cardiovascular events for observational studies and net clinical events for RCTs. Four RCTs and 17 observational studies with a total of 38,741 patients were included. Net clinical events were more common with unchanged DAPT than with de-escalation in RCTs [odd ratio (OR): 1.71; 95% confidence interval (CI), 1.21–2.43; I2= 69.4%], which was mainly due to higher risks of any bleeding (OR: 1.81; 95% CI, 1.14–2.88; I2= 75.5%) and major bleeding (OR: 1.58; 95% CI, 1.02–2.46; I2= 0), without significant differences in ischaemic events. However, trial sequential analysis revealed that sufficient information was obtained just for net clinical events, not for respective ischaemic or bleeding events in RCTs. In the analysis based on real-world observational studies, the risks of myocardial infarction (OR: 0.77; 95% CI, 0.61–0.98; I2= 0) and stroke (OR: 0.42; 95% CI, 0.22–0.81; I2= 0) were lower with the unchanged DAPT group. Therefore, de-escalation of DAPT led to a marked reduction in net clinical events compared with unchanged DAPT in RCTs, which was mainly due to reduced bleeding events. However, sufficient information for ischaemic events was not obtained. In the analysis based on real-world observational studies, myocardial infarction and stroke were more common with de-escalation, which should arise our attention.

Since current culture model of red swamp crayfish (Procambarus clarkii) is mainly rice-shrimp co-culture model, the use of pesticide is inevitable. As a broad-spectrum pesticide, abamectin is widely used in aquaculture. Thus, it is importanrt to study the toxicity of abamectin to P. clarkii.The previous studies of our laboratory showed that with increasing of abamectin concentration, the molting frequency of P. clarkiiincreased but growth slowed down. We speculated that it was related to energy metabolism. This study attempted to explore the effect of abamectin on energy metabolism of P. clarkiiby analyzing TCA cycle. The results showed that the response mechanisms of TCA cycle to abamectin in P. clarkiiwere different in hepatopancreas and gills. Due to the different absorption and accumulation rates of toxic substances in hepatopancreas and gills, the biochemical indexes and genes expression levels of hepatopancreas decreased with the increasing of abamectin concentration, while the indexes increased in gills. And the continuous abamectin stress could also cause irreversible damage to gills. As an important hub of lipid-, glucose-, and amino acid-metabolism, once TCA cycle was blocked, the growth of P. clarkiiwas slow, the immunity and the reproductive capacity were decreased. This study provided a guidance for healthy culture of P. clarkii, and a theoretical basis for further study on energy metabolism of crustaceans.

Magnesium (Mg) deficiency is associated with increased risk and malignancy in colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here, we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2Cand ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial–mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142pup-regulated MMP2 and enhanced cell migration, while treatment with MgCl2reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+attenuated the DBN1–ACTN4 interaction by decreasing DBN1S142p, which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.

To identify relationships between busulfan (Bu) exposure and outcomes of a cohort pediatric patients receiving hematopoietic stem cell transplantation (HSCT), along with a targeted busulfan-based conditioning regimen. We retrospectively evaluated targeted busulfan concentrations in 53 pediatric patients (age 0.4–16 years) who received busulfan 4 times daily according to recommended weight-based doses in a single-center analysis between 2018 and 2020. In this trial, individual busulfan pharmacokinetics were performed following dose 5 of the conditioning regimen. Twenty four of 53 patients (45.3%) studies did not require dose adjustments. Equal number of patients (24/53) required one dose adjustments while two-dose adjustment applied for 5 of 53 (9.4%). Twenty-one percent of the patients exhibited ll-lV aGVHD. The incidence of veno-occlusive disease (VOD) was in 3.8% of the 53 patients, while incidence of hemorrhagic cystitis (II–III) reached to 9.7%. Engraftment was successful in 98% of the 53 patients with relapse in 2% of cases. The probability of overall survival and disease-free survival at day 100 was 96% and 94%, respectively. In conclusion, therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.

Optical holography capable of the complete recording and reconstruction of light’s wavefront, plays significant roles on interferometry, microscopy, imaging, data storage, and three-dimensional displaying. Conventional holography treats light as scalar field with only phase and intensity dimensions, leaving the polarization information entirely neglected. Benefiting from the multiple degrees of freedom (DOFs) for optical field manipulation provided by the metasurface, vectorial holography with further versatile control in both polarization states and spatial distributions, greatly extended the scope of holography. As full vectorial nature of light field has been considered, the information carried out by light has dramatically increased, promising for novel photonic applications with high performance and multifarious functionalities. This review will focus on recent advances on vectorial holography empowered by multiple DOFs metasurfaces. Interleaved multi-atom approach is first introduced to construct vectorial holograms with spatially discrete polarization distributions, followed by the versatile vectorial holograms with continuous polarizations that are designed usually by modified iterative algorithms. We next discuss advances with further spectral response, leading to vivid full-color vectorial holography; and the combination between the far-field vectorial wavefront shaping enabled by vectorial holography and the near-field nano-printing functionalities by further exploiting local polarization and structure color responses of the meta-atom. The development of vectorial holography provides new avenues for compact multi-functional photonic devices, potentially useful in optical encryption, anticounterfeiting, and data storage applications.

Gold nanoparticles (AuNPs) colorimetric assays based on distance-dependent optical characteristics have been widely employed for bioanalysis. However, this assay is not effective for visually detecting low-concentration targets due to the faint color change. Here, we developed a handheld nano-centrifugal device which could separate the crosslinked and non-crosslinked AuNPs. Results showed that the handheld nano-centrifugal device could easily reach more than 6000 r/min within 10 s simply by stretching and tightening the coiled rope in an appropriate rhythm. Further, combined with the CRISPR/Cas12a nucleic acids recognition system, a field-deployable colorimetric platform termed handheld nano-centrifugal device assisted CRISPR/Cas12a (Hand-CRISPR) has been validated. Moreover, clinical diagnostics applications for Epstein-Barr virus (EBV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection with high sensitivity and accuracy (100% consistency with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) test results) have been demonstrated. Overall, the Hand-CRISPR platform showed great promise in point-of-care-test (POCT) application, expected to become a powerful supplement to the standard nucleic acid testing method in remote or poverty-stricken areas.

The pursuit of tranquility experience has emerged as a new demand in tourism, but the perception of tranquility in tourism remains understudied. Although there are tools in the psychology and acoustics to measure tranquility perception, they are not suitable in tourism research. Therefore, this paper attempts to explore two contextual tourists’ perceptions scale of tranquility by analyzing two distinct destinations. Visual, auditory, and tactile involvement were introduced into the scale construction. A total of 1012 samples were collected from rural tranquil area and desert tranquil area. Following dimension construction and item production, EFA, CFA, reliability and validity tests were performed. Finally, a five-dimensional tranquility perception scale was developed. This study enriches the current themes and perspectives of multisensory involvement in the tranquility research and directs for further research on tourism, culture and tranquility experience.

Enhancing endocannabinoid signaling produces anxiolytic- and antidepressant-like effects, but the neural circuits involved remain poorly understood. The medial habenula (MHb) is a phylogenetically-conserved epithalamic structure that is a powerful modulator of anxiety- and depressive-like behavior. Here, we show that a robust endocannabinoid signaling system modulates synaptic transmission between the MHb and its sole identified GABA input, the medial septum and nucleus of the diagonal band (MSDB). With RNAscope in situ hybridization, we demonstrate that key enzymes that synthesize or degrade the endocannabinoids 2-arachidonylglycerol (2-AG) or anandamide are expressed in the MHb and MSDB, and that cannabinoid receptor 1 (CB1) is expressed in the MSDB. Electrophysiological recordings in MHb neurons revealed that endogenously-released 2-AG retrogradely depresses GABA input from the MSDB. This endocannabinoid-mediated depolarization-induced suppression of inhibition (DSI) was limited by monoacylglycerol lipase (MAGL) but not by fatty acid amide hydrolase. Anatomic and optogenetic circuit mapping indicated that MSDB GABA neurons monosynaptically project to cholinergic neurons of the ventral MHb. To test the behavioral significance of this MSDB–MHb endocannabinoid signaling, we induced MSDB-specific knockout of CB1 or MAGL via injection of virally-delivered Cre recombinase into the MSDB of Cnr1loxP/loxPor MgllloxP/loxPmice. Relative to control mice, MSDB-specific knockout of CB1 or MAGL bidirectionally modulated 2-AG signaling in the ventral MHb and led to opposing effects on anxiety- and depressive-like behavior. Thus, depression of synaptic GABA release in the MSDB-ventral MHb pathway may represent a potential mechanism whereby endocannabinoids exert anxiolytic and antidepressant-like effects.

The Nazarov electrocyclization reaction is a convenient, widely used method for construction of cyclopentenones. In the past few decades, catalytic asymmetric versions of the reaction have been extensively studied, but the strategies used to control the position of the double bond limit the substituent pattern of the products and thus the synthetic applications of the reaction. Herein, we report highly enantioselective silicon-directed Nazarov reactions which were cooperatively catalyzed by a Lewis acid and a chiral Brønsted acid. The chiral cyclopentenones we synthesized using this method generally cannot be obtained by means of other catalytic enantioselective reactions, including previously reported methods for enantioselective Nazarov cyclization. The silicon group in the dienone substrate stabilized the β-carbocation of the intermediate, thereby determining the position of the double bond in the product. Mechanistic studies suggested that the combination of Lewis and Brønsted acids synergistically activated the dienone substrate and that the enantioselectivity of the reaction originated from a chiral Brønsted acid promoted proton transfer reaction of the enol intermediate.

In order to reduce the immunoreactivity of sarcoplasmic calcium-binding protein (SCP), site-directed mutations were used to replace key amino acids in the conformational epitopes and calcium-binding sites. The mutant SCPs (mSCPs) were expressed in Escherichia coli, and their immunoreactivities were analyzed using iELISA and basophil activation assays. Furthermore, the structural changes of mSCPs were determined from the circular dichroism spectra. The iELISA results showed that mSCPs could effectively inhibit the binding of wild-type SCP (wtSCP) to sensitive serum, with inhibition rates that reached 90%. Moreover, mSCPs could downregulate the expression levels of CD63 and CD203c on the basophil surface. Compared with wtSCP, the peak values were significantly changed, and the calcium binding ability was impaired, which explained the decline in immunoreactivities of the mSCPs. All of the data confirmed that this approach was effective in reducing the immunoreactivity of SCP and could be applied to other shellfish allergens.

Glassy carbon (GC) is a type of non-graphitizing disordered carbon material at ambient pressure and high temperatures, which has been widely used due to its excellent mechanical properties. Here we report the changes in the microstructure and mechanical properties of GC treated at high pressures (up to 5 GPa) and high temperatures. The formation of intermediate sp2–sp3phases is identified at moderate treatment temperatures before the complete graphitization of GC, by analyzing synchrotron X-ray diffraction, Raman spectra, and transmission electron microscopy images. The intermediate metastable carbon materials exhibit superior mechanical properties with hardness reaching up to 10 GPa and compressive strength reaching as high as 2.5 GPa, nearly doubling those of raw GC, and improving elasticity and thermal stability. The synthesis pressure used in this study can be achieved in the industry on a commercial scale, enabling the scalable synthesis of this type of strong, hard, and elastic carbon materials.

Although tremendous effort has been devoted to the development of methods for iron catalysis, few of the catalysts reported to date exhibit clear superiority to other metal catalysts, and the mechanisms of most iron catalysis remain unclear. Herein, we report that iron complexes bearing 2,9-diaryl-1,10-phenanthroline ligands exhibit not only unprecedented catalytic activity but also unusual ligand-controlled divergent regioselectivity in hydrosilylation reactions of various alkynes. The hydrosilylation protocol described herein provides a highly efficient method for preparing useful di- and trisubstituted olefins on a relatively large scale under mild conditions, and its use markedly improved the synthetic efficiency of a number of bioactive compounds. Mechanistic studies based on control experiments and density functional theory calculations were performed to understand the catalytic pathway and the observed regioselectivity.

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays a critical role in many fundamental cellular processes. We recently reported that PP6 is essential for female fertility. Here, we report that PP6 is involved in meiotic recombination and that germ cell-specific deletion of PP6 by Stra8-Crecauses defective spermatogenesis. The PP6-deficient spermatocytes were arrested at the pachytene stage and defects in DSB repair and crossover formation were observed, indicating that PP6 facilitated meiotic double-stranded breaks (DSB) repair. Further investigations revealed that depletion of PP6 in the germ cells affected chromatin relaxation, which was dependent on MAPK pathway activity, consequently preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. Taken together, our results demonstrate that PP6 has an important role in meiotic recombination and male fertility.