Quasi van der Waals Epitaxy of Single Crystalline GaN on Amorphous SiO2/Si(100) for Monolithic Optoelectronic Integration.

The realization of high quality (0001) GaN on Si(100) is paramount importance for the monolithic integration of Si-based integrated circuits and GaN-enabled optoelectronic devices. Nevertheless, thorny issues including large thermal mismatch and distinct crystal symmetries typically bring about uncontrollable polycrystalline GaN formation with considerable surface roughness on standard Si(100). Here a breakthrough of high-quality single-crystalline GaN film on polycrystalline SiO2/Si(100) is presented by quasi van der Waals epitaxy and fabricate the monolithically integrated photonic chips. The in-plane orientation of epilayer is aligned throughout a slip and rotation of high density AlN nuclei due to weak interfacial forces, while the out-of-plane orientation of GaN can be guided by multi-step growth on transfer-free graphene. For the first time, the monolithic integration of light-emitting diode (LED) and photodetector (PD) devices are accomplished on CMOS-compatible SiO2/Si(100). Remarkably, the self-powered PD affords a rapid response below 250 µs under adjacent LED radiation, demonstrating the responsivity and detectivity of 2.01 × 105 A/W and 4.64 × 1013 Jones, respectively. This work breaks a bottleneck of synthesizing large area single-crystal GaN on Si(100), which is anticipated to motivate the disruptive developments in Si-integrated optoelectronic devices.

Efficient Strategy for Radiative Cooling Based on Ultra-Broad-Band Infrared Regulation of Flexible Bilayer Film.

Flexible thermal radiation films with adjustable broad-band infrared radiation could maintain various heat-generating electronic devices working stably in corresponding operating temperatures, making them good candidates for radiative cooling (RC) material. However, the controllable radiation peaks of the metamaterial were narrow, and manipulation was a time-consuming and complex process. Herein, we design a simple TiN/Si bilayer film with controllable broad-band radiation peaks at a thermal radiation wavelength of 3.5-20 µm by impedance matching. Meanwhile, the different bilayer films applied to aluminum devices at different temperatures exhibit outstanding heat dissipation efficiency and maintain the corresponding equilibrium temperature to ensure that devices work stably for a long time. Moreover, the bilayer films deposited on the flexible PI substrates exhibit preferable thermostability and higher tensile strength than existing radiative cooling materials deposited on PDMS, PE, PMMA or TPX, etc. This work provides an effective strategy to realize efficient radiation cooling for flexible electronic devices and spacecraft appendages.

Glycogen synthase kinase-3ß mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein.

BACKGROUND: Glycogen synthase kinase-3ß (GSK3ß), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I/R) injury. METHODS: The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group n = 6) and P12 cells oxygen-glucose deprivation/reoxygenation (OGD/R) model was analyzed using short hairpin GSK3ß lentivirus and overexpression of FTO lentivirus (in vitro), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3ß, FTO, TLR4 expression, and GSK3ß activity, respectively. RESULTS: After GSK3ß knockdown in the OGD/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3ß reversed the OGD/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3ß in vivo, the reduction of FTO in mice suffering from MCAO was reversed. CONCLUSIONS: Our research shows that GSK3ß/FTO/TLR4 pathway contributes to cerebral I/R injury.

Enantiospecific Synthesis of Aniline-Derived Sulfonimidamides.

Reaction of sulfonimidoyl fluorides with anilines and Ca(NTf2)2 results in the formation of chiral sulfonimidamides. The reaction proceeds with inversion of the stereocenter at a sulfur atom. Enantiospecificity of the reaction was observed for all studied non-heterocyclic anilines. Combined experimental and computational mechanistic studies highlight chelate-type coordination of the sulfonimidoyl group to Ca(NTf2)2 and the formation of a SN2-like transition state, in which leaving F- coordinates with the Ca2+ ion.

A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems.

The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications.

A Study on THE Mechanism of Electroacupuncture to Alleviate Visceral Pain and NGF Expression.

Visceral pain is unbearable, and natural methods are needed to relieve it. Electroacupuncture is a relatively new technique that helps relieve visceral pain by improving blood circulation and providing energy to clogged parts of the body. However, its analgesic effect and mechanism in colorectal pain are still unknown. In this study, the visceral pain models of electroacupuncture in rats were compared and discussed, using nanocomponents to stimulate the expression and mechanism of the nerve growth factor in colorectal pain and electroacupuncture and to observe the expression and mechanism of nerve growth factor in visceral pain relief rats induced by nanocomponents and electroacupuncture. The results show that nanocomponents can effectively relieve visceral pain under the action of electroacupuncture. NGF can activate endogenous proliferation, migration, differentiation, and integration. NSC can promote nerve regeneration and recovery after injury.

A small-molecule inhibitor and degrader of the RNF5 ubiquitin ligase.

RNF5 E3 ubiquitin ligase has multiple biological roles and has been linked to the development of severe diseases such as cystic fibrosis, acute myeloid leukemia, and certain viral infections, emphasizing the importance of discovering small-molecule RNF5 modulators for research and drug development. The present study describes the synthesis of a new benzo[b]thiophene derivative, FX12, that acts as a selective small-molecule inhibitor and degrader of RNF5. We initially identified the previously reported STAT3 inhibitor, Stattic, as an inhibitor of dislocation of misfolded proteins from the endoplasmic reticulum (ER) lumen to the cytosol in ER-associated degradation. A concise structure-activity relationship campaign (SAR) around the Stattic chemotype led to the synthesis of FX12, which has diminished activity in inhibition of STAT3 activation and retains dislocation inhibitory activity. FX12 binds to RNF5 and inhibits its E3 activity in vitro as well as promoting proteasomal degradation of RNF5 in cells. RNF5 as a molecular target for FX12 was supported by the facts that FX12 requires RNF5 to inhibit dislocation and negatively regulates RNF5 function. Thus, this study developed a small-molecule inhibitor and degrader of the RNF5 ubiquitin ligase, providing a chemical biology tool for RNF5 research and therapeutic development.

Sulfur-Phenolate Exchange: SuFEx-Derived Dynamic Covalent Reactions and Degradation of SuFEx Polymers.

The products of the SuFEx reaction between sulfonimidoyl fluorides and phenols, sulfonimidates, are shown to display dynamic covalent chemistry with other phenols. This reaction was shown to be enantiospecific, finished in minutes at room temperature in high yields, and useful for both asymmetric synthesis and sustainable polymer production. Its wide scope further extends the usefulness of SuFEx and related click chemistries.

Targeting CAR and Nrf2 improves cyclophosphamide bioactivation while reducing doxorubicin-induced cardiotoxicity in triple-negative breast cancer treatment.

Cyclophosphamide (CPA) and doxorubicin (DOX) are key components of chemotherapy for triple-negative breast cancer (TNBC), although suboptimal outcomes are commonly associated with drug resistance and/or intolerable side effects. Through an approach combining high-throughput screening and chemical modification, we developed CN06 as a dual activator of the constitutive androstane receptor (CAR) and nuclear factor erythroid 2-related factor 2 (Nrf2). CN06 enhances CAR-induced bioactivation of CPA (a prodrug) by provoking hepatic expression of CYP2B6, while repressing DOX-induced cytotoxicity in cardiomyocytes in vitro via stimulating Nrf2-antioxidant signaling. Utilizing a multicellular coculture model incorporating human primary hepatocytes, TNBC cells, and cardiomyocytes, we show that CN06 increased CPA/DOX-mediated TNBC cell death via CAR-dependent CYP2B6 induction and subsequent conversion of CPA to its active metabolite 4-hydroxy-CPA, while protecting against DOX-induced cardiotoxicity by selectively activating Nrf2-antioxidant signaling in cardiomyocytes but not in TNBC cells. Furthermore, CN06 preserves the viability and function of human iPSC-derived cardiomyocytes by modulating antioxidant defenses, decreasing apoptosis, and enhancing the kinetics of contraction and relaxation. Collectively, our findings identify CAR and Nrf2 as potentially novel combined therapeutic targets whereby CN06 holds the potential to improve the efficacy/toxicity ratio of CPA/DOX-containing chemotherapy.

Configurationally Chiral SuFEx-Based Polymers.

Novel methods to make synthetic chiral polymers are highly desirable given their potential in a rapidly increasing number of bio-inspired applications. The enantiospecific sulfur-fluorine exchange (SuFEx) reaction of chiral di-sulfonimidoyl fluorides (di-SFs) with diphenols, was used to produce high-molecular-weight chiral polymers with configurational backbone chirality. The resulting new class of polymers, polysulfonimidates, can be efficiently produced via this step-growth mechanism for a wide range of di-SFs and diphenols, yielding MnPS up to 283 kDa with a typical dispersity D around 1.6. The optical activity of the resulting chiral polymers is largely due to the intrinsic asymmetry of the S atoms (configurational chirality). Finally, the enantiospecificity (ee>98 %) of the polymerization reaction was demonstrated by the degradation of a disulfide-containing polysulfonimidate. This novel route towards configurational main-chain chirality opens up new approaches towards tailor-made chiral polymers with precisely defined properties.

SuFExable polymers with helical structures derived from thionyl tetrafluoride.

Sulfur(VI) fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulfur(VI) connective hubs. The efficiency of SuFEx and the stability of the resulting bonds have led to polymer chemistry applications. Now, we report the SuFEx click chemistry synthesis of several structurally diverse SOF4-derived copolymers based on the polymerization of bis(iminosulfur oxydifluorides) and bis(aryl silyl ethers). This polymer class presents two key characteristics. First, the [-N=S(=O)F-O-] polymer backbone linkages are themselves SuFExable and undergo precise SuFEx-based post-modification with phenols or amines to yield branched functional polymers. Second, studies of individual polymer chains of several of these new materials indicate helical polymer structures. The robust nature of SuFEx click chemistry offers the potential for post-polymerization modification, enabling the synthesis of materials with control over composition and conformation.

The Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Catheter-Related Bladder Discomfort in Patients Undergoing Transurethral Resection of the Prostate.

BACKGROUND: Catheter-related bladder discomfort (CRBD), an extremely distressing complication secondary to an indwelling urinary catheterization, is frequently reported in patients with transurethral resection of the prostate (TURP), postoperatively. A prospective, randomized, controlled, double-blind study was designed to assess the efficacy of transcutaneous electrical acupoint stimulation (TEAS) as a treatment for CRBD in patients undergoing TURP. METHODS: Seventy benign prostatic hyperplasia male patients undergoing TURP under general anesthesia requiring intraoperative urinary catheterization were enrolled for the trial. An experienced acupuncturist performed TEAS for 30 minutes before general anesthesia with acupoints RN7, RN6, RN5, RN4, and RN3 and bilateral BL32, BL33, and BL34. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SPO2), body temperature (T), and blood samples were collected during the surgery. A series of assessments included the incidence and severity of CRBD, postoperative pain, nausea and vomiting, and physical and mental state measurements. RESULTS: The incidence of CRBD was significantly lower in TEAS group than in control group at the time T5 [9(26%) vs. 28(80%), P < 0.001], T9 [20(57%) vs. 28(80%), P=0.039], T11 [7(20%) vs. 31(89%), P < 0.001], and T12 [4(11%) vs. 7(20%), P=0.003]. The severity of CRBD was significantly lower in TEAS group than in control group at the time T5 [0 vs. 10 (29%), P < 0.001], T9 [2(6%) vs. 10(29%), P=0.011], and T11 [0 vs .9(26%), P=0.002]. The QoR-40 total score was higher in TEAS group at time T11 [191.7(4.4) vs. 189.1(4.3), P=0.007] and T12 [195.3(1.9) vs. 193.3(3.0), P < 0.001]. The postoperative analgesia requirement was higher in control group [5.0(2.9) vs. 3.8(1.9), P=0.045]. CONCLUSIONS: TEAS could significantly prevent the incidence and severity of CRBD, reduce the postoperative analgesic requirement in the early postoperative period, and promote the quality of early recovery in patients undergoing TURP.

Enantioselective Construction of 2-Aryl-2,3-dihydrobenzofuran Scaffolds Using Cu/SPDO-Catalyzed [3 + 2] Cycloaddition.

A new, efficient approach toward the preparation of 2-aryl-2,3-dihydrobenzofuran scaffolds through the Cu/SPDO-catalyzed [3 + 2] cycloaddition between quinone ester and styrene derivatives has been developed. The procedure features excellent enantioselectivities (up to 99% ee), high yields (up to 96%), and broad substrate tolerance. Additionally, asymmetric synthesis of natural corsifurans A and B from commercially available starting materials has also been achieved in two or three steps using this reaction as a key transformation.

Comparison between Tramadol and Butorphanol for Treating Postoperative Catheter-Related Bladder Discomfort: A Randomized Controlled Trial.

BACKGROUND: Intraoperative catheterization often leads to postoperative catheter-related bladder discomfort (CRBD) during the restoration period. This study aimed to assess the curative effect of butorphanol as a K receptor agonist in the treatment of postoperative CRBD. Patients and Approaches. Sixty patients with CRBD who underwent elective nonurological surgery at the postanesthesia care unit were randomly and evenly assigned to two groups. The control group was slowly injected with tramadol 1.5 mg/kg using a Murphy dropper, whereas the experimental group was intravenously injected with butorphanol 0.02 mg/kg. Severity, pain score, and sedation score of CRBD were evaluated at 0 min, 5 min, 15 min, 30 min, 1 h, and 6 h later. RESULTS: The severity score of CRBD and visual analog scale pain score were lower in the butorphanol group than in the control group, whereas the sedation score was higher in the butorphanol group than in the control group. CONCLUSION: Butorphanol relieves on postoperative urination discomfort and pain compared with tramadol.

The effect of prophylactic rewarming on postoperative nausea and vomiting among patients undergoing laparoscopic hysterectomy: a prospective randomized clinical study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication from general anesthesia that impacts on postoperative recovery. OBJECTIVE: To evaluate prophylactic rewarming following general anesthesia, so as to decrease the incidence of PONV among patients undergoing laparoscopic hysterectomy. DESIGN AND SETTING: Prospective randomized clinical study at a hospital in China. METHODS: Sixty-two patients were randomly assigned into two groups. The forced air warming (FAW) group received pre-warmed Ringer's solution with FAW until the end of surgery. The control group received Ringer's solution without FAW. The pre-warmed Ringer's solution was stored in a cabinet set at 40 °C. The FAW tube was placed beside the patient's shoulder with a temperature of 43 °C. RESULTS: Sixty patients completed the study. The FAW group showed significant differences versus the controls regarding temperature. At 6, 24 and 48 hours postoperatively, the incidences of PONV were 53.3%, 6.7% and 3.3% in the FAW group versus 63.3%, 30% and 3.3% in the controls. VAS scores were significantly lower in the FAW group than in the controls at 24 hours (P= 0.035). Forty-item questionnaire total scores in the FAW group were significantly higher than in the controls. The physical independence and pain scores at 24 hours and emotional support and pain scores at 48 hours in the FAW group were higher than in the controls (P < 0.05). There was no difference in hemodynamics or demographics between the two groups (P > 0.05). CONCLUSIONS: Prophylactic rewarming relieved PONV and improved the quality of postoperative recovery. CHINESE CLINICAL TRIAL REGISTER (CHICTR): ChiCTR-IOR-17012901.

Catalytic Enantioselective Synthesis and Switchable Chiroptical Property of Inherently Chiral Macrocycles.

We report herein a strategy to construct enantiopure inherently chiral macrocycles, ABCD-type heteracalix[4]aromatics, through a catalytic enantioselective intramolecular C-N bond forming reaction. A chiral ligand-palladium complex was found to efficiently induce the inherent chirality of molecules during the macrocyclization process with ee values up to >99%. The resulting ABCD-type heteracalix[4]aromatics displayed excellent and pH-triggered switchable electronic circular dichroism and circularly polarized luminescence properties.

Quasi-2D Growth of Aluminum Nitride Film on Graphene for Boosting Deep Ultraviolet Light-Emitting Diodes.

Efficient and low-cost production of high-quality aluminum nitride (AlN) films during heteroepitaxy is the key for the development of deep ultraviolet light-emitting diodes (DUV-LEDs). Here, the quasi-2D growth of high-quality AlN film with low strain and low dislocation density on graphene (Gr) is presented and a high-performance 272 nm DUV-LED is demonstrated. Guided by first-principles calculations, it is found that AlN grown on Gr prefers lateral growth both energetically and kinetically, thereby resulting in a Gr-driven quasi-2D growth mode. The strong lateral growth mode enables most of dislocations to annihilate each other at the AlN/Gr interface, and therefore the AlN epilayer can quickly coalesce and flatten the nanopatterned sapphire substrate. Based on the high quality and low strain of AlN film grown on Gr, the as-fabricated 272 nm DUV-LED shows a 22% enhancement of output power than that with low-temperature AlN buffer, following a negligible wavelength shift under high current. This facile strategy opens a pathway to drastically improve the performance of DUV-LEDs.

Silicon-Free SuFEx Reactions of Sulfonimidoyl Fluorides: Scope, Enantioselectivity, and Mechanism.

SuFEx reactions, in which an S-F moiety reacts with a silyl-protected phenol, have been developed as powerful click reactions. In the current paper we open up the potential of SuFEx reactions as enantioselective reactions, analyze the role of Si and outline the mechanism of this reaction. As a result, fast, high-yielding, "Si-free" and enantiospecific SuFEx reactions of sulfonimidoyl fluorides have been developed, and their mechanism shown, by both experimental and theoretical methods, to yield chiral products.

Analyses of mRNA-seq and miRNA-seq of the brain reveal the sex differences of gene expression and regulation before and during gonadal differentiation in 17ß-estradiol or 17α-methyltestosterone-induced olive flounder (Paralichthys olivaceus).

Olive flounder (Paralichthys olivaceus) is a commercially important flatfish species cultured in East Asia. Female flounders generally grow more rapidly than males, therefore control of the sex ratio seems to be a proposed way to increase production. However, the sex determination gene and sex determination mechanism have yet been elucidated. The brain is an important organ that is involved in gonadal development. To explore the sex differences of gene expression in the brain before and during the flounder gonadal differentiation, we used messenger RNA (mRNA)-seq technology to investigate transcriptomes of male and female brains. Between female and male brains, 103 genes were differentially expressed before ovarian differentiation, 16 genes were differentially expressed before testicular differentiation, and 64 genes were differentially expressed during gonadal differentiation. According to annotation and Kyoto Encyclopedia of Genes and Genomes information, the differentially expressed genes (DEGs) were involved in circadian rhythm, circadian rhythm-fly, circadian entrainment, dopaminergic synapse, calcium signaling, glutamatergic synapse, taste transduction, herpes simplex infection, long-term depression, retrograde endocannabinoid signaling, and the synaptic vesicle cycle pathways. MicroRNA (miRNA)-seq was performed during the gonadal differentiation and the target genes of miRNAs were predicted. Integrated analysis of mRNA-seq and miRNA-seq showed that 29 of the 64 DEGs were regulated by the differentially expressed miRNAs during the gonadal differentiation. Our study provides a basis for further studies of brain sex differentiation and the molecular mechanism of sex determination in olive flounder.

Roles of forkhead box protein L2 (foxl2) during gonad differentiation and maintenance in a fish, the olive flounder (Paralichthys olivaceus).

As an important maricultured fish, the olive flounder Paralichthys olivaceus shows sex-dimorphic growth. Thus, the molecular mechanisms involved in sex control in P. olivaceus have attracted researchers' attention. Among the sex-related genes, forkhead box protein L2 (foxl2) exhibits significant sex-dimorphic expression patterns and plays an important role in fish gonad differentiation and development. The present study first investigated the expression levels and promoter methylation dynamics of foxl2 during flounder gonad differentiation under treatments of high temperature and exogenous 17ß-oestradiol (E2). During high temperature treatment, the expression of flounder foxl2 may be repressed via maintenance of DNA methylation. Then, flounder with differentiated testis at Stages I-II were treated with exogenous 5ppm E2 or 5ppm E2+150ppm trilostane (TR) to investigate whether exogenous sex hormones could induce flounder sex reversal. The differentiated testis exhibited phenotypic variations of gonadal dysgenesis with upregulation of female-related genes (foxl2 and cytochrome P450 family 19 subfamily A (cyp19a)) and downregulation of male-related genes (cytochrome P450 family 11 subfamily B member 2 (cyp11b2), doublesex- and mab-3 related transcription factor 1 (dmrt1), anti-Mullerian hormone (amh) and SRY-box transcription factor 9 (sox9)). Furthermore, a cotransfection assay of the cells of the flounder Sertoli cell line indicated that Foxl2 was able alone or with nuclear receptor subfamily 5 group A member 2 (Nr5a2) jointly to upregulate expression of cyp19a. Moreover, Foxl2 and Nr5a2 repressed the expression of dmrt1. In summary, Foxl2 may play an important role in ovarian differentiation by maintaining cyp19a expression and antagonising the expression of dmrt1. However, upregulation of foxl2 is not sufficient to induce the sex reversal of differentiated testis.