Revisiting Aromatic Claisen Rearrangement Using Unstable Aryl Sulfonium/Iodonium Species: The Strategy of Breaking Up the Whole into Parts.

Since Ludwig Claisen's discovery of the sigmatropic rearrangement of allyl aryl ethers in 1912, aromatic Claisen rearrangement has continuously attracted the attention of both experimental and theoretical chemists. Over more than a century of growth, this protocol has proven to be a practical and powerful synthetic tool in many aspects. However, the reaction scope has long been limited to aryl ethers and their S or N analogs until the serendipitous discovery of aromatic iodonium-Claisen rearrangement by Oh et al. in 1988 and the development of aromatic sulfonium-Claisen rearrangement by Kita et al. in 2004. Unlike traditional Claisen rearrangements, these hypervalent-bonding-based Claisen-type rearrangements can be performed by simply mixing electrophilically activated aryl sulfoxides/iodanes with certain nucleophiles to directly deliver rearrangement products. In addition to the simple operation, remarkable features, such as readily available substrates, valuable products and intriguing rearrangement patterns, have led to a dramatic resurgence of this rearrangement chemistry.In this Account, we summarize our recent works on developing new aromatic rearrangement modes using sulfonium/iodonium reagents. Interestingly, the program started with an accidental discovery that aryl sulfoxides could be coupled with alkyl nitriles in the presence of Tf2O and base. Mechanistic studies reveal that the reaction proceeds in three major steps, including the Tf2O-triggered assembly of both coupling partners, base-promoted deprotonation of in situ-generated aryl sulfonium-imine species leading to a key rearrangement precursor called aryl sulfonium-ketenimine species, and subsequent facile and rapid [3,3]-rearrangement. On the basis of the mechanistic underpinning, we divided the one-step operation into two steps called the "assembly/deprotonation" protocol for constructing unstable rearrangement precursors. Most notably, the switch from the commonly used one-step to mechanism-based multiple-step manipulation, which can be termed "breaking up the whole into parts", not only enables the independent control of each step of the reaction, thus significantly expanding the accessible synthetic scope, but also raises opportunities for developing new rearrangement patterns. For example, the "assembly/deprotonation" protocol has also been applied to the development of [5,5]-rearrangement of aryl sulfoxides and the asymmetric rearrangement of aryl iodanes, thus enabling the unprecedented regio- and stereocontrol of the rearrangement process. Furthermore, the "breaking up the whole into parts" thinking triggered us to merge the Morita-Baylis-Hillman (MBH) reaction into the rearrangement process to accomplish Z-selective MBH-type [3,3]-rearrangement of α,ß-unsaturated nitriles and E-selective MBH-type [3,3]-rearrangement of α,ß-unsaturated 2-oxazolines, which expands the scope of rearrangement partners to include α,ß-unsaturated carbonyls. In addition, the impressive rapidity of the rearrangement process found in our initial discovery has also been recognized as a congestion-acceleration effect, which was further utilized to forge the rapid ortho-cyanoalkylative rearrangement of aryl iodanes, and thus leading to the first dearomatization of aryl iodanes. We anticipate that our protocols and ideas behind the methods will be complementary to the traditional thinking of the aromatic Claisen rearrangement.

Analysis of long noncoding RNAs in the aqueous humor of wet age-related macular degeneration.

Wet age-related macular degeneration (wAMD) is the main cause of irreversible blindness in the elderly, and its pathogenesis is still not fully understood. Long non-coding RNAs (lncRNAs) participated in the pathogenesis of a number of neovascular diseases, but their role in wAMD is less known. In order to reveal the potential role of lncRNAs in wAMD, we used high-throughput sequencing to assess lncRNAs and mRNAs expression profile in the aqueous humor of patients with wAMD and of patients with age-related cataract as control. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify the potential biological functions and signaling pathways of RNA. A coding-non-coding gene co-expression (CNC) network was constructed to identify the interaction of lncRNAs and mRNAs. Quantitative PCR was used to validate the expression of selected lncRNAs. We identified 1071 differentially expressed lncRNAs and 3658 differentially expressed mRNAs in patients with wAMD compared to controls. GO and KEGG analyses suggested that differentially expressed lncRNAs-coexpressed mRNAs were mainly enriched in Rab GTPase binding, GTPase activation, RAS signaling pathway and autophagy. The top 100 differentially expressed genes were selected to build the CNC network, which could be connected by 416 edges. LncRNAs are differentially expressed in the aqueous humor of patients with wAMD and they are involved in several pathogenetic pathways. These dysregulated lncRNAs and their target genes could represent promising therapeutic targets in wAMD.

Rapid screening of polybrominated diphenyl ethers in water by solid-phase microextraction coupled with ultrahigh-resolution mass spectrometry.

Polybrominated diphenyl ethers (PBDEs) are considered emerging organic contaminants that attract more attention in the environment. Herein, online coupling of solid-phase microextraction and ultrahigh-resolution mass spectrometry was developed for rapid screening of eight PBDEs in water samples. This procedure was completed in 22 min, about 6 times faster than the routine workflow such as solid-phase extraction coupled with gas chromatography-mass spectrometry. Thermal desorption and solvent-assisted atmospheric pressure chemical ionization were developed for the effective coupling of solid-phase microextraction (SPME) with ultrahigh-resolution mass spectrometry (UHRMS), which contributed to the signal enhancement and made the methodology feasible for environmental screening. The limits of detection and quantification were 0.01-0.50 ng/mL and 0.05-4.00 ng/mL, respectively. The recoveries were 57.2-75.2% for quality control samples at spiking levels of 0.8-10 ng/mL (4-50 ng/mL for BDE209), with relative standard deviation less than 19.0%. Twelve water samples from different river sites near industrial areas were screened using the developed method. The results showed that BDE-209 was the dominant PBDE (1.02-1.28 ng/mL in positive samples), but its amount was lower than the human health ambient water quality criteria. Consequently, the developed method provides a rapid and reliable way of evaluating contamination status and risks of PBDEs in aqueous environment.

Defluorinative Multi-Functionalization of Fluoroaryl Sulfoxides Enabled by Fluorine-Assisted Temporary Dearomatization.

Owing to its unique physical properties, fluorine is often used to open up new reaction channels. In this report, we establish a cooperation of [5,5]-rearrangement and fluorine-assisted temporary dearomatization for arene multi-functionalization. Specifically, the [5,5]-rearrangement of fluoroaryl sulfoxides with ß,γ-unsaturated nitriles generates an intriguing dearomatized sulfonium species which is short-lived but exhibits unusually high electrophilicity and thus can be instantly trapped by nucleophiles and dienes at a remarkably low temperature (-95 °C) to produce four types of valuable multi-functionalized benzenes, respectively, involving appealing processes of defluorination, desulfurization, and sulfur shift. Mechanistic studies indicate that the use of fluorine on arenes not only circumvents the generally inevitable [3,3]-rearrangement but also impedes the undesired rearomatization process, thus provides a precious space for constructing and elaborating the temporarily dearomatized fluorinated sulfonium species.

Rapid and simultaneous detection of multiple pathogens in the lower reproductive tract during pregnancy based on loop-mediated isothermal amplification-microfluidic chip.

BACKGROUND: Female reproductive tract infection (RTI) is the common source of varied diseases, especially as an important risk factor for pregnancy outcomes, therefore the rapid, accurate and simultaneous detection of multiple pathogens is in urgent need for assisting the diagnosis and treatment of RTI in pregnant women. Streptococcus agalactiae (S. agalactiae), Enterococcus faecalis (E. faecalis), Gardnerella vaginalis (G. vaginalis), Candida albicans (C. albicans) and Chlamydia trachomatis (C. trachomatis) are five main pathogens in lower genital tract with high risk, serious consequences and clinical demands. The combination of loop-mediated isothermal amplification (LAMP) and microfluidic technology was used to develop the LAMP-microfluidic chip for rapid, simple, sensitive and simultaneous detection of the five target pathogens above. RESULTS: Standard strains and clinical isolates were used for the establishment of the novel LAMP method in tube and LAMP-microfluidic chip, followed by the chip detection on 103 clinical samples and PCR verification partially. The sensitivities of LAMP of S. agalactiae, E. faecalis, G. vaginalis, and C. albicans in tube were 22.0, 76.0, 13.2, 1.11 CFU/µL, respectively, and C. trachomatis was 41.3 copies/µL; on LAMP-microfluidic chip they were 260, 154, 3.9 and 7.53 CFU/µL, respectively, and C. trachomatis was 120 copies/µL. The positive coincidence rates of clinical stains in tube and on chip experiments were 100%. Compared with the classic culture method performed in hospitals, the positive coincidence rate of the 103 clinical samples detected by LAMP-microfluidic chip were 100%. For the six inconsistent ones, including four G. vaginalis and two C. albicans positive samples tested by LAMP-microfluidic chip and verified by PCR were negative by culturing method in hospitals, indicating the lack of efficient detection by the classic culturing method. CONCLUSION: Our study suggested that the LAMP-microfluidic chips could simultaneously, efficiently, and accurately detect multiple main pathogens, including S. agalactiae, E. faecalis, G. vaginalis, C. albicans and C. trachomatis, in clinical samples of female RTI to give a great clinical value. Accordingly, this novel method has the potential to provide a valuable reference for female RTI screening and early diagnosis during pregnancy.

Advances in the Understanding of the Complex Role of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up-to-date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Functional and Mechanistic Studies of Two Anti-coccidial Herbs, Bidens pilosa and Artemisia indica.

Currently, antibiotics are commonly used to treat coccidiosis, a severe protozoal disease in chickens. However, due to growing concerns about the antibiotic residue in meat and eggs, phytogenic formulations are becoming an attractive approach to manage this disease. In this study, we investigated the anti-coccidial function and mechanism of phytogenic formulations composed of Bidens pilosa, Artemisia indica, and both used in combination. We found that these formulations increased the survival rate and reduced body weight loss, the feed conversion ratio, oocyst excretion, bloody stools, and gut lesions of chickens. Mechanistic studies showed that A. indica, but not B. pilosa, reduced the survival of Eimeria oocysts. Accordingly, they both inhibited oocyst sporulation and sporozoite invasion into Madin-Darby bovine kidney (MDBK) cells. Overall, we demonstrate that these formulations protect chickens against coccidiosis. Moreover, a combination of B. pilosa and A. indica has an additive effect on coccidiosis control and growth performance in chickens compared to either one used alone.

Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila.

BACKGROUND: The anticancer drug camptothecin (CPT), first isolated from Camptotheca acuminata, was subsequently discovered in unrelated plants, including Ophiorrhiza pumila. Unlike known monoterpene indole alkaloids, CPT in C. acuminata is biosynthesized via the key intermediate strictosidinic acid, but how O. pumila synthesizes CPT has not been determined. RESULTS: In this study, we used nontargeted metabolite profiling to show that 3α-(S)-strictosidine and 3-(S), 21-(S)-strictosidinic acid coexist in O. pumila. After identifying the enzymes OpLAMT, OpSLS, and OpSTR as participants in CPT biosynthesis, we compared these enzymes to their homologues from two other representative CPT-producing plants, C. acuminata and Nothapodytes nimmoniana, to elucidate their phylogenetic relationship. Finally, using labelled intermediates to resolve the CPT biosynthesis pathway in O. pumila, we showed that 3α-(S)-strictosidine, not 3-(S), 21-(S)-strictosidinic acid, is the exclusive intermediate in CPT biosynthesis. CONCLUSIONS: In our study, we found that O. pumila, another representative CPT-producing plant, exhibits metabolite diversity in its central intermediates consisting of both 3-(S), 21-(S)-strictosidinic acid and 3α-(S)-strictosidine and utilizes 3α-(S)-strictosidine as the exclusive intermediate in the CPT biosynthetic pathway, which differs from C. acuminata. Our results show that enzymes likely to be involved in CPT biosynthesis in O. pumila, C. acuminata, and N. nimmoniana have evolved divergently. Overall, our new data regarding CPT biosynthesis in O. pumila suggest evolutionary divergence in CPT-producing plants. These results shed new light on CPT biosynthesis and pave the way towards its industrial production through enzymatic or metabolic engineering approaches.

Morita-Baylis-Hillman-Type [3,3]-Rearrangement: Switching from Z- to E-Selective α-Arylation by New Rearrangement Partners.

α-aryl α,ß-unsaturated carbonyls represent an important class of derivatizable synthetic intermediates, however, the synthesis of such compounds still remains a challenge. Recently, we showcased a novel Z-selective α-arylation of α,ß-unsaturated nitriles with aryl sulfoxides via [3,3]-rearrangement involving an Morita-Baylis-Hillman (MBH) process. Herein, we demonstrate the feasibility of reversing the stereoselectivity of such MBH-type [3,3]-rearrangement by switching to a new pair of rearrangement partners consisting of aryl iodanes and α,ß-unsaturated oxazolines. As a result, the two protocols complement each other in approaching E- or Z-α-aryl α,ß-unsaturated carbonyl derivatives. Mechanistic studies reveal a possible reaction pathway and provide an explanation for the opposite stereoselectivities.

Z-Selective α-Arylation of α,ß-Unsaturated Nitriles via [3,3]-Sigmatropic Rearrangement.

The Morita-Baylis-Hillman (MBH) reaction and [3, 3]-sigmatropic rearrangement are two paradigms in organic synthesis. We have merged the two types of reactions to achieve [3,3]-rearrangement of aryl sulfoxides with α,ß-unsaturated nitriles. The reaction was achieved by sequentially treating both coupling partners with electrophilic activator (Tf2 O) and base, offering an effective approach to prepare synthetically versatile α-aryl α,ß-unsaturated nitriles with Z-selectivity through direct α-C-H arylation of unmodified α,ß-unsaturated nitriles. The control experiments and DFT calculations support a four-stage reaction sequence, including the assembly of Tf2 O activated aryl sulfoxide with α,ß-unsaturated nitrile, MBH-like Lewis base addition, [3,3]-rearrangement, and E1cB-elimination. Among these stages, the Lewis base addition is diastereoselective and E1cB-elimination is cis-selective, which could account for the remarkable Z-selectivity of the reaction.

Asymmetric Iodonio-[3,3]-Sigmatropic Rearrangement to Access Chiral α-Aryl Carbonyl Compounds.

Here we describe an asymmetric [3,3]-sigmatropic rearrangement of aryl iodanes that enables the enantioselective α-arylation of chiral 2-oxazolines, thereby producing valuable chiral α-aryl carbonyl compounds. The success of this protocol hinges on the selective assembly of aryl iodanes with 2-oxazolines and the smooth deprotonation of the in situ-generated iodonium-imine species. The nearly neutral and mild conditions of the reaction allow it to tolerate a wide variety of functional groups. Moreover, the remaining iodine atom in the products not only provides a versatile platform for further elaboration of such molecules but also supplies the asymmetric hypervalent iodine chemistry with a new class of chiral scaffolds.

Selective [5,5]-Sigmatropic Rearrangement by Assembly of Aryl Sulfoxides with Allyl Nitriles.

Aromatic [5,5]-sigmatropic rearrangement is an appealing protocol for accessing 1,4-substituted arenes. However, such a protocol has not been well utilized in organic synthesis because of the difficulties in the synthesis of the substrates, selectivity issues, and limited substrate scope. Described herein is a new [5,5]-sigmatropic reaction utilizing readily available aryl sulfoxides and allyl nitriles. This reaction features mild reaction conditions, high chemo- and regioselectivity, excellent functional-group compatibility, and broad substrate scope. Computational studies suggest that the success of the reaction can be attributed to the selective electrophilic assembly of the rearrangement precursors, in which a linear -C=C=N- linkage favors [5,5]-sigmatropic rearrangement over the competitive [3,3]-sigmatropic rearrangement.

Comorbidities and mortality risk in COVID-19 patients with congestive heart failure: A comprehensive analysis.

The COVID-19 pandemic has posed unprecedented challenges to global healthcare systems, resulting in alarming incidence and mortality rates among patients with comorbidities, including heart failure. Understanding the characteristics of heart failure and other comorbidities during the COVID-19 pandemic is crucial for effective prevention and treatment. However, the current understanding of these characteristics among different racial groups remains incomplete. In this study, we investigated a cohort of 4711 patients, classifying them into congestive heart failure (CHF) and non-CHF groups. Biomarker analysis revealed noteworthy variations in blood urea nitrogen, aspartate aminotransferase, and white blood cell levels based on the presence or absence of CHF. Stratified by three racial groups, univariate logistic regression analysis identified significant differences in multiple variables, including CHF. Subsequent univariate Cox regression and Kaplan-Meier analysis demonstrated variations in mortality factors among distinct populations, with age and comorbidity playing prominent roles. This study utilized a large-scale database to investigate the characteristics of heart failure and related variables during the COVID-19 pandemic. The findings revealed distinctive mortality risk factors among various racial groups, emphasizing the significance of customized risk assessment and management approaches for diverse populations. These findings also provide a valuable resource for the development of targeted interventions and the promotion of equitable healthcare outcomes in the context of the COVID-19 pandemic.

Retinal and choroidal microvascular features during pregnancy: a systematic review and meta-analysis.

PURPOSE: To analyse retinal and choroidal microvasculature features in healthy pregnant women using optical coherence tomography angiography (OCTA). METHODS: PubMed, Embase, Ovid, Web of Science and Cochrane Library were searched for published studies that compare retinal and choroidal microvasculature characteristics between pregnant females and non-pregnant females from inception to November 2023. The statistics were continuous variables. They were presented as the mean difference (MD) with a corresponding 95% CI. We used Review Manager software 5.4.1 for statistical analysis. RESULTS: A total of 5 eligible studies involving 219 eyes in the pregnancy group and 186 eyes in the control group were included in the meta-analysis. The pooled results showed that the retinal deep capillary plexus vascular density (DCP VD) measured by OCTA was significantly higher in healthy pregnant women than in controls (MD 1.53; 95% CI 0.62 to 2.44; I2=0%; p=0.0009). However, differences between the two groups in the retinal superficial capillary plexus VD (SCP VD) (MD 0.41;95% CI -1.26 to 2.09; I2=85%; p=0.63), the foveal avascular zone (FAZ) (MD 0.01; 95% CI -0.01 to 0.03; I2=14%; p=0.18), the choriocapillaris VD (CC VD) (MD 0.76; 95% CI -1.11 to 2.64; I2=79%; p=0.43) were uncertain. CONCLUSIONS: Our meta-analysis found that the DCP VD of healthy pregnant women was higher than that of non-pregnant controls. However, differences in SCP VD, FAZ and CC VD between the healthy pregnant women and the non-pregnancy controls were uncertain. Our findings can help to get a deeper understanding of retinal and choroidal microvascular characteristics during pregnancy.

mm3DSNet: multi-scale and multi-feedforward self-attention 3D segmentation network for CT scans of hepatobiliary ducts.

Image segmentation is a key step of the 3D reconstruction of the hepatobiliary duct tree, which is significant for preoperative planning. In this paper, a novel 3D U-Net variant is designed for CT image segmentation of hepatobiliary ducts from the abdominal CT scans, which is composed of a 3D encoder-decoder and a 3D multi-feedforward self-attention module (MFSAM). To well sufficient semantic and spatial features with high inference speed, the 3D ConvNeXt block is designed as the 3D extension of the 2D ConvNeXt. To improve the ability of semantic feature extraction, the MFSAM is designed to transfer the semantic and spatial features at different scales from the encoder to the decoder. Also, to balance the losses for the voxels and the edges of the hepatobiliary ducts, a boundary-aware overlap cross-entropy loss is proposed by combining the cross-entropy loss, the Dice loss, and the boundary loss. Experimental results indicate that the proposed method is superior to some existing deep networks as well as the radiologist without rich experience in terms of CT segmentation of hepatobiliary ducts, with a segmentation performance of 76.54% Dice and 6.56 HD.

Validation of reliability, repeatability and consistency of three-dimensional choroidal vascular index.

This study aimed to investigate the reliability, repeatability and consistency of choroidal vascularity index (CVI) measurements provided by an artificial intelligence-based software in swept-source optical coherence tomography (SS-OCT) in normal subject, and to evaluate the influencing factors for 3D-CVI. Repeatability of 3D-CVI by SS-OCT was evaluated based on different scanning modes including Macular Cubes (3 mm × 3 mm, 6 mm × 6 mm, 9 mm × 9 mm) and Optic Nerve Head 6 mm × 6 mm. Intraclass Correlation Coefficient (ICC) was used to estimate the repeatability and reproducibility of five repeated measurement by SS-OCT. Consistency of CVI between SS-OCT and spectral-domain optical coherence tomography (SD-OCT) was measured and compared in a pilot study of ten eyes and agreement between SS-OCT and SD-OCT was evaluated by Bland-Altman analysis and Deming regression. The influencing factors for 3D-CVI including age, gender, axial length and spherical equivalent on CVI was further investigated in a prospective study of 125 eyes of 125 healthy subjects. ICC between different measurements by SS-OCT was 0.934 (95% CI 0.812-0.956) indicating good repeatability. Intraclass correlation coefficient between CVI measure by SS-OCT and SD-OCT was 0.887 (95% CI 0.796-0.938, P value < 0.001). The mean difference between 3D-CVI measured by SS-OCT and SD-OCT 0.133. CVI measured with SS-OCTA showed stronger correlations with axial length and age but not correlated with gender. There is good agreement between CVIs obtained from the built-in software that requires less timing in manual quantification. Studies investigating choroidal vascularity can be standardized by the AI-based CVI analyze software.

Blood-brain barrier disruption and hemorrhagic transformation in acute stroke before endovascular reperfusion therapy.

Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.

Blood-Brain Barrier Disruption and Imaging Assessment in Stroke.

Disruption of the blood-brain barrier (BBB) is an important pathological hallmark of ischemic stroke. Blood-brain barrier disruption (BBBD) is a consequence of ischemia and may also exacerbate damage to brain parenchyma. Therefore, maintaining BBB integrity is critical for the central nervous system (CNS) homeostasis. This review offers a concise overview of BBB structure and function, along with the mechanisms underlying its impairment following a stroke. In addition, we review the recent imaging techniques employed to study blood-brain barrier permeability (BBBP) in the context of ischemic brain injury with the goal of providing imaging guidance for stroke diagnosis and treatment from the perspective of the BBBD. This knowledge is vital for developing strategies to safeguard the BBB during cerebral ischemia.

PROST: quantitative identification of spatially variable genes and domain detection in spatial transcriptomics.

Computational methods have been proposed to leverage spatially resolved transcriptomic data, pinpointing genes with spatial expression patterns and delineating tissue domains. However, existing approaches fall short in uniformly quantifying spatially variable genes (SVGs). Moreover, from a methodological viewpoint, while SVGs are naturally associated with depicting spatial domains, they are technically dissociated in most methods. Here, we present a framework (PROST) for the quantitative recognition of spatial transcriptomic patterns, consisting of (i) quantitatively characterizing spatial variations in gene expression patterns through the PROST Index; and (ii) unsupervised clustering of spatial domains via a self-attention mechanism. We demonstrate that PROST performs superior SVG identification and domain segmentation with various spatial resolutions, from multicellular to cellular levels. Importantly, PROST Index can be applied to prioritize spatial expression variations, facilitating the exploration of biological insights. Together, our study provides a flexible and robust framework for analyzing diverse spatial transcriptomic data.

Transcriptome analyses reveal photosynthesis-related genes involved in photosynthetic regulation under low temperature stress in Lavandula angustifolia Mill.

In order to reveal the mechanisms of photosynthetic regulation of Lavandula angustifolia Mill. under low temperature stress, photosynthesis-related genes were screened and the molecular mechanism were analyzed for this species growing in Harbin, northeast of China. RNA-seq technique and photosynthetic physiology measurement were performed under 20°C, 10°C, and 0°C in this study. The results showed that the observing modified rectangular hyperbola mode could accurately reflect the light-response processes under low temperature stress and the low temperature reduced the light energy utilization of L. angustifolia. The stomatal conductance decreased with the temperature dropping, which was associated with the up-regulation of LaBAM1s, LaMPK4-1 and LaMMK2. The up-regulation of LaMPK4-1 and LaMMK2 was beneficial for ROS scavenging. The improvement of cold resistance in L. angustifolia was related to the up-regulated expression of LaFBA and LaOMTs and down-regulated expression of LaGAPAs, LaGOX, and LaTKL1s with the temperature decreasing. The up-expression of LaPSY at 10°C than it at 20°C could protect the photosynthetic organs from oxidative damage. Moreover, the photosynthetic rates at 10°C and 0°C were close to the measured values, which was related to the interactions of RCA with SBPase and Rubisco with SBPase. These findings could provide a theoretical reference for further exploring the cold tolerance mechanism of L. angustifolia, as an important aromatic plant resource, and promoting its cultivation and distribution in the northeast of China.