Synthesis of Bridged Cycloisoxazoline Scaffolds via Rhodium-Catalyzed Coupling of Nitrones with Cyclic Carbonate.

Bridged isoxazolidines were synthesized via Rh(III)-catalyzed C-H allylation of α-aryl nitrones with 5-methylene-1,3-dioxan-2-one. The nitrone group serves as a directing group and 1,3-dipole in the C-H activation/[3 + 2] cycloaddition cascade, exhibiting excellent chemo- and stereoselectivity along with good functional group compatibility. The resulting skeletal structure was conveniently modified to produce a range of important chemical frameworks, and the protocol was applied to biologically active molecules.

Integrated Sensor-Optics Communication System Using Bidirectional Fiber and FSO Channels and Hybrid Deep Learning Techniques.

This paper introduces a new bidirectional integration approach that combines fiber sensor/free space optics (FSO) communication using an intensity and wavelength division multiplexer (IWDM) techniques-based long-distance fiber Bragg grating (FBG) sensor strain-sensing system. By implementing coarse wavelength division multiplexing (CWDM), the system achieves the simultaneous transmission of optical communication and fiber optical sensor (FOS) sensing signals, resulting in a highly capable, flexible, and cost-effective solution. The proposed FSO transmission technique addresses complex fiber cable installation concerns with topographical limitations. This bidirectional structure ensures the reliability and stability of the long-distance FBG sensor system, supported by extensive research and experimentation. A hybrid stacked gated recurrent units and long short-term memory (SGRU-LSTM) model is proposed to enhance strain measurement accuracy by predicting and measuring the central wavelength of overlapped strain-sensing FBG sensor signals. The results demonstrate the superiority of the proposed model in peak wavelength detection accuracy. The primary benefit of integrating communication and sensing is the significant reduction in construction costs by eliminating the requirement for two individual fiber optic systems, as the integration allows for a single system to fulfill both functions, resulting in more efficient and cost-effective implementation. Overall, this paper contributes to advancing long-distance FBG sensor systems by integrating fiber sensor/FSO communication and deep learning techniques, improving transmission distance, multiplexing capacity, measurement accuracy, system survivability, and cost-effectiveness.

Rhodium-Catalyzed Atroposelective Construction of Indoles via C-H Bond Activation.

Reported herein is the rhodium(III)-catalyzed C-H activation of anilines bearing an N-isoquinolyl directing group for oxidative [3+2] annulation with four classes of internal alkynes, leading to atroposelective indole synthesis via dynamic kinetic annulation with C-N reductive elimination constituting the stereo-determining step. This reaction proceeds under mild conditions with high regio- and enantioselectivity and functional group compatibility.

Rhodium-Catalyzed Enantioselective Synthesis of ß-Amino Alcohols via Desymmetrization of gem-Dimethyl Groups.

Desymmetrization of gem-dimethyl groups en route to the rhodium(III)-catalyzed enantioselective sp3 C-H amidation is reported. Synthetically important ß-amino alcohol derivatives were accessed in moderate to good yields and high enantioselectivity. The high enantioselectivity is enabled by an appropriate oxime directing group, sterically biased gem-groups in the C-H substrate, and high reactivity of the amidating reagent.

Toxic effects of arsenic trioxide on spermatogonia are associated with oxidative stress, mitochondrial dysfunction, autophagy and metabolomic alterations.

Arsenic is a toxic metalloid that can cause male reproductive malfunctions and is widely distributed in the environment. The aim of this study was to investigate the cytotoxicity of arsenic trioxide (ATO) induced GC-1 spermatogonial (spg) cells. Our results found that ATO increased the levels of catalase (CAT) and malonaldehyde (MDA) and reactive oxygen species (ROS), while decreasing glutathione (GSH) and the total antioxidant capacity (T-AOC). Therefore, ATO triggered oxidative stress in GC-1 spg cells. In addition, ATO also caused severe mitochondrial dysfunction that included an increase in residual oxygen consumption (ROX), and decreased the routine respiration, maximal and ATP-linked respiration (ATP-L-R), as well as spare respiratory capacity (SRC), and respiratory control rate (RCR); ATO also damaged the mitochondrial structure, including mitochondrial cristae disordered and dissolved, mitochondrial vacuolar degeneration. Moreover, degradation of p62, LC3 conversion, increasing the number of acidic vesicle organelles (AVOs) and autophagosomes and autolysosomes are demonstrated that the cytotoxicity of ATO may be associated with autophagy. Meanwhile, the metabolomics analysis results showed that 20 metabolites (10 increased and 10 decreased) were significantly altered with the ATO exposure, suggesting that maybe there are the perturbations in amino acid metabolism, lipid metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins. We concluded that ATO was toxic to GC-1 spg cells via inducing oxidative stress, mitochondrial dysfunction and autophagy as well as the disruption of normal metabolism. This study will aid our understanding of the mechanisms behind ATO-induced spermatogenic toxicity.

Rhodium(III)-Catalyzed C-H Activation of Nitrones and Annulative Coupling with Nitroalkenes.

Rh(III)-catalyzed synthesis of nitro-functionalized indenes has been realized via C-H activation of arylnitrones and annulation with nitroolefins. The reaction proceeded in moderate to high yields with good functional group tolerance under ambient atmosphere.

Rhodium(III)-catalyzed alkenylation reactions of 8-methylquinolines with alkynes by C(sp3)-H activation.

The alkenylation reactions of 8-methylquinolines with alkynes, catalyzed by [{Cp*RhCl2}2], proceeds efficiently to give 8-allylquinolines in good yields by C(sp(3))-H bond activation. These reactions are highly regio- and stereoselective. A catalytically competent five-membered rhodacycle has been structurally characterized, thus revealing a key intermediate in the catalytic cycle.

Synthesis of Spirocyclohexadienones via Palladium-Catalyzed Dearomatization of Dibenzoxaborins.

The development of Pd(II)-catalyzed dearomatization transformation of dibenzoxaborins with alkynes triggered by transmetalation from boron to palladium has been achieved, leading to the synthesis of spirocyclohexadienones, an important skeleton demonstrating potential biomedical utility. The [3 + 2] spiroannulation exhibits remarkable regioselectivity and broad substrate scope under mild reaction conditions. This methodology employs dibenzoxaborin as a substrate to establish the formal dearomatization of 2-phenylphenol, which poses a formidable energy barrier to the destruction of aromaticity.

Geographical distribution and ecological niche dynamics of Crassostrea sikamea (Amemiya, 1928) in China's coastal regions under climate change.

Global climate change drives species redistribution, threatening biodiversity and ecosystem heterogeneity. The Kumamoto oyster, Crassostrea sikamea (Amemiya, 1928), one of the most promising aquaculture species because of its delayed reproductive timing, was once prevalent in southern China. In this study, an ensemble species distribution model was employed to analyze the distribution range shift and ecological niche dynamics of C. sikamea along China's coastline under the current and future climate scenarios (RCP 2.6-8.5 covering 2050 s and 2100 s). The model results indicated that the current habitat distribution for C. sikamea consists of a continuous stretch extending from the coastlines of Hainan Province to the northern shores of Jiangsu Province. By the 2050 s, the distribution range will stabilize at its southern end along the coast of Hainan Province, while expanding northward to cover the coastal areas of Shandong Province, showing a more dramatic trend of contraction in the south and invasion in the north by the 2100 s. In RCP8.5, the southern end retracts to the coasts of Guangdong, whereas the northern end covers all of China's coastal areas north of 34°N. C. sikamea can maintain relatively stable ecological niche characteristics, while it may occupy different ecological niche spaces under future climate conditions. Significant niche expansion will occur in lower temperature. We concluded C. sikamea habitats are susceptible to climate change. The rapid northward expansion of C. sikamea may open new possibilities for oyster farming in China, but it will also have important consequences for the ecological balance and biodiversity of receiving areas. It's imperative that we closely examine and strategize to address these repercussions for a win-win situation.

A comprehensive AI model development framework for consistent Gleason grading.

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

Ru(II)-Catalyzed One-Pot Synthesis of 1,2-Hydropyridines via a Three-Component Reaction.

A ruthenium(II)-catalyzed one-pot synthesis of highly substituted 1,2-dihydropyridines (DHPs) via a three-component reaction system has been realized. The reaction is conducted using a simple Ru(II) catalyst without the addition of specific ligands. The catalytic system exhibits good functionality tolerance with a wide range of starting materials. The DHPs obtained can be easily converted into tetrahydropyridines and azabicyclo[4.2.0]octa-4,7-dienes by subsequent reduction or [2 + 2] cycloaddition reaction.

Asymmetric [5+1] Annulation via C-H Activation/1,4-Rh Migration/Double Bond Shift Using a Transformable Pyridazine Directing Group.

N-Heterocycle-assisted C-H activation/annulation reactions have provided new concepts for the construction and transformation of azacycles. In this work, we disclose a [5+1] annulation reaction using a novel transformable pyridazine directing group (DG). The DG-transformable reaction mode led to the construction of a new heterocyclic ring accompanied by transformation of the original pyridazine directing group via a C-H activation/1,4-Rh migration/double bond shift pathway, affording the skeleton of pyridazino[6,1-b]quinazolines with a good substrate scope under mild conditions. Diverse fused cyclic compounds can be achieved by derivatization of the product. The asymmetric synthesis of the skeleton was also realized to afford the enantiomeric products with good stereoselectivity.

Rhodium-catalyzed cascade oxidative annulation leading to substituted naphtho[1,8-bc]pyrans by sequential cleavage of C(sp2)-H/C(sp3)-H and C(sp2)-H/O-H bonds.

The cascade oxidative annulation reactions of benzoylacetonitrile with internal alkynes proceed efficiently in the presence of a rhodium catalyst and a copper oxidant to give substituted naphtho[1,8-bc]pyrans by sequential cleavage of C(sp(2))-H/C(sp(3))-H and C(sp(2))-H/O-H bonds. These cascade reactions are highly regioselective with unsymmetrical alkynes. Experiments reveal that the first-step reaction proceeds by sequential cleavage of C(sp(2))-H/C(sp(3))-H bonds and annulation with alkynes, leading to 1-naphthols as the intermediate products. Subsequently, 1-naphthols react with alkynes by cleavage of C(sp(2))-H/O-H bonds, affording the 1:2 coupling products. Moreover, some of the naphtho[1,8-bc]pyran products exhibit intense fluorescence in the solid state.

RhodiumIII-catalyzed remote difunctionalization of arenes assisted by a relay directing group.

Rhodium-catalyzed diverse tandem twofold C-H bond activation reactions of para-olefin-tethered arenes have been realized, with unsaturated reagents such as internal alkynes, dioxazolones, and isocyanates being the coupling partner as well as a relay directing group which triggers cyclization of the para-olefin group under oxidative or redox-neutral conditions. The reaction proceeded via initial ortho-C-H activation assisted by a built-in directing group in the arene, and the ortho-incorporation of the unsaturated coupling partner simultaneously generated a relay directing group that allows sequential C-H activation at the meta-position and subsequent cyclization of the para-olefins. The overall reaction represents C-C or N-C difunctionalization of the arene with the generation of diverse 2,3-dihydrobenzofuran platforms. The catalytic system proceeded with good efficiency, simple reaction conditions, and broad substrate scope. The diverse transformations of the products demonstrated the synthetic utility of this tandem reaction.

The potential risks of herbicide butachlor to immunotoxicity via induction of autophagy and apoptosis in the spleen.

Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1ß, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.

Rh(III)-Catalyzed Annulation of 2-Biphenylboronic Acid with Diverse Activated Alkenes.

Rhodium(III)-catalyzed annulation of 2-biphenylboronic acids with three classes of activated alkenes has been realized, leading to the synthesis of fused or bridged cyclic skeletons via transmetalation-initiated C-H activation. In the annulative coupling of 2-biphenylboronic acid with a CF3-substituted enone, the bulky cyclopentadienyl ligand (CptBu) in the catalyst proved effective to promote the reductive elimination process prior to protonolysis, affording the [4 + 2] annulated products instead of the simple 1,4-addition product. Seven-membered rings were obtained when disubstituted cyclopropenones were employed. Bridged cycles were isolated from the coupling of 2-biphenylboronic acid with benzoquinones as a result of 2-fold Michael additions. The substrate scopes were found to be broad with up to 99% yield under air-tolerant conditions.

Rhodium(iii)-catalyzed asymmetric [4+1] spiroannulations of O-pivaloyl oximes with α-diazo compounds.

Chiral RhIII catalysts can catalyze the asymmetric [4+1] spiroannulation of O-pivaloyl oximes with α-diazo homophthalimides under redox-neutral and acid/base-neutral conditions, leading to formation of chiral spirocyclic imines as a result of C-H activation and N-O cleavage. The reaction proceeded with high efficiency and features broad substrate scope, mild reaction conditions, and high to excellent enantioselectivities.

The hepatotoxicity of altrazine exposure in mice involves the intestinal microbiota.

Atrazine (ATR), a bio accumulative herbicide is frequently used in agriculture to control unwanted weeds. Due to continuous application, atrazine persists in the environment and causes deleterious impacts including neurotoxicity, hepatotoxicity, and gut microbiota disorders. Therefore, this study for the first time reports the variation in the gut microbiota, induction of process of apoptosis and autophagy in mice induced by ATR. Results indicated that TUNEL-positive hepatocytes suggestive of apoptosis were increased in livers of different experimental mice. Results on metabolic analysis in liver tissues indicated an overall change in seventy-six metabolites particularly Uridine 5'-diphosphate, Propenoylcarnitine and Chinenoside V resulting in generation of energy-related metabolic disorders and imbalance of oxidation/autoxidation status. Results on gut microbiome inquisition showed that ATR changed the richness and diversity of gut microbiota of mice and number of Firmicutes. Moreover, results also revealed that ATR induced apoptosis via disruption of apoptotic (Bax, Bcl2, and Casp3) and autophagy (LC3/Map1lc3a, Beclin 1/Becn1 and P62/Sqstm1) genes. Results of our experimental study confirmed that changes in gut microbiota play a significant role in process of gut immune regulation and inflammation via different metabolites. In conclusion, the findings of our study provide a new idea for the involvement of mechanisms of detoxification in liver and inquisition of gut microbiota plays crucial role in regulation of physiological activities through liver-gut axis to mitigate toxic effects in animals.

Acetyl-L-Carnitine Induces Autophagy to Promote Mouse Spermatogonia Cell Recovery after Heat Stress Damage.

Acetyl-L-carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal-induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC-1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 µM ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T-AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis-related genes (Bcl-2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy-related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC-1 cells after heat stress.

Exposure to the herbicide butachlor activates hepatic stress signals and disturbs lipid metabolism in mice.

Butachlor is a systemic herbicide widely applied on wheat, rice, beans, and different other crops, and is frequently detected in groundwater, surface water, and soil. Therefore, it is necessary to investigate the potential adverse health risks and the underlying mechanisms of hepatotoxicity caused by exposure to butachlor in invertebrates, other nontarget animals, and public health. For this reason, a total of 20 mice were obtained and randomly divided into two groups. The experimental mice in one group were exposed to butachlor (8 mg/kg) and the mice in control group received normal saline. The liver tissues were obtained from each mice at day 21 of the trial. Results indicated that exposure to butachlor induced hepatotoxicity in terms of swelling of hepatocyte, disorders in the arrangement of hepatic cells, increased concentrations of different serum enzymes such as alkaline phosphate (ALP) and aspartate aminotransferase (AST). The results on the mechanisms of liver toxicity indicated that butachlor induced overexpression of Apaf-1, Bax, Caspase-3, Caspase-9, Cyt-c, p53, Beclin-1, ATG-5, and LC3, whereas decreases the expression of Bcl-2 and p62 suggesting abnormal processes of apoptosis and autophagy. Results on different metabolites (61 differential metabolites) revealed upregulation of PE and LysoPC, whereas downregulation of SM caused by butachlor exposure in mice led to the disruption of glycerophospholipids and lipid metabolism in the liver. The results of our experimental research indicated that butachlor induces hepatotoxic effects through disruption of lipid metabolism, abnormal mechanisms of autophagy, and apoptosis that provides new insights into the elucidation of the mechanisms of hepatotoxicity in mice induced by butachlor.