Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

From sky to road: Incorporating the satellite imagery into analysis of freight truck-related crash factors.

Freight truck-related crashes in urban contexts have caused significant economic losses and casualties, making it increasingly essential to understand the spatial patterns of such crashes. Limitations regarding data availability have greatly undermined the generalizability and applicability of certain prior research findings. This study explores the potential of emerging geospatial data to delve deeply into the determinants of these incidents with a more generalizable research design. By synergizing high-resolution satellite imagery with refined GIS map data and geospatial tabular data, a rich tapestry of the road environment and freight truck operations emerges. To navigate the challenges of zero-inflated issues of the crash datasets, the Tweedie Gradient Boosting model is adopted. Results reveal a pronounced spatial heterogeneity between highway and urban non-highway road networks in crash determinants. Factors such as freight truck activity, intricate road network patterns, and vehicular densities rise to prominence, albeit with varying degrees of influence across highways and urban non-highway terrains. Results emphasize the need for context-specific interventions for policymakers, encompassing optimized urban planning, infrastructural overhauls, and refined traffic management protocols. This endeavor may not only elevate the academic discourse around freight truck-related crashes but also champion a data-driven approach towards safer road ecosystems for all.

Exo-Selective Diels-Alder Reactions.

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule". While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo-Diels-Alder reactions often considered outliers. This review delves into recent examples of exo-Diels-Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s-cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo-Diels-Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels-Alder reactions.

Exercise intervention for patients with chronic low back pain: a systematic review and network meta-analysis.

Purpose: Chronic low back pain (CLBP) is an aging and public health issue that is a leading cause of disability worldwide and has a significant economic impact on a global scale. Treatments for CLBP are varied, and there is currently no study with high-quality evidence to show which treatment works best. Exercise therapy has the characteristics of minor harm, low cost, and convenient implementation. It has become a mainstream treatment method in clinics for chronic low back pain. However, there is insufficient evidence on which specific exercise regimen is more effective for chronic non-specific low back pain. This network meta-analysis aimed to evaluate the effects of different exercise therapies on chronic low back pain and provide a reference for exercise regimens in CLBP patients. Methods: We searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to 10 May 2022. Inclusion and exclusion criteria were used for selection. We collected information from studies to compare the effects of 20 exercise interventions on patients with chronic low back pain. Results: This study included 75 randomized controlled trials (RCTs) with 5,254 participants. Network meta-analysis results showed that tai chi [standardized mean difference (SMD), -2.11; 95% CI, -3.62 to -0.61], yoga (SMD, -1.76; 95% CI -2.72 to -0.81), Pilates exercise (SMD, -1.52; 95% CI, -2.68, to -0.36), and sling exercise (SMD, -1.19; 95% CI, -2.07 to -0.30) showed a better pain improvement than conventional rehabilitation. Tai chi (SMD, -2.42; 95% CI, -3.81 to -1.03) and yoga (SMD, -2.07; 95% CI, -2.80 to -1.34) showed a better pain improvement than no intervention provided. Yoga (SMD, -1.72; 95% CI, -2.91 to -0.53) and core or stabilization exercises (SMD, -1.04; 95% CI, -1.80 to -0.28) showed a better physical function improvement than conventional rehabilitation. Yoga (SMD, -1.81; 95% CI, -2.78 to -0.83) and core or stabilization exercises (SMD, -1.13; 95% CI, -1.66 to -0.59) showed a better physical function improvement than no intervention provided. Conclusion: Compared with conventional rehabilitation and no intervention provided, tai chi, toga, Pilates exercise, sling exercise, motor control exercise, and core or stabilization exercises significantly improved CLBP in patients. Compared with conventional rehabilitation and no intervention provided, yoga and core or stabilization exercises were statistically significant in improving physical function in patients with CLBP. Due to the limitations of the quality and quantity of the included studies, it is difficult to make a definitive recommendation before more large-scale and high-quality RCTs are conducted.

Synthesis towards Phainanoid F: Photo-induced 6π-Electrocyclization for Constructing Contiguous All-Carbon Quaternary Centers.

In this paper, we report an efficient strategy for synthesizing the DEFGH rings of phainanoid F. The key to the construction of the 13,30-cyclodammarane skeleton of the molecule was a photo-induced 6π-electrocyclization and a homoallylic elimination. Notably, this is a rare example of using electrocyclization reaction to simultaneously construct two vicinal quaternary carbons in total synthesis. The strategy outlined here forms the basis of our total synthesis of Phainanoid F, and it could also serve as a generally applicable approach for synthesizing other natural products containing similar 13,30-cyclodammarane skeletons.

Synthesis of Polysubstituted Furans via Rh(II)-Catalyzed [2 + 3] Annulation of N-Sulfonyl-1,2,3-triazoles with Enaminones.

An unprecedented [2 + 3] annulation of N-sulfonyl-1,2,3-triazoles with enaminones is reported for the access of polysubstituted furans. The key to the success of the transformations lies in the use of Rh(II)-Brønsted acid as cooperative catalysts. Unlike the conventional annulations of N-sulfony-l-1,2,3-triazoles, the Rh(II)-azavinyl carbenes species play dual functions in this work, enabled by the cleavage of the C(sp2)-N bond. The mechanism studies suggested that an intermolecular rearrangement of the TsNH- group is crucial to the annulation process.

Mueller matrix imaging polarimeter at the wavelength of 265 nm.

Mueller matrix imaging polarimeters (MMIPs) have been developed in the wavelength region of >400n m with great potential in many fields yet leaving a void of instrumentation and application in the ultraviolet (UV) region. For the first time to our knowledge, an UV-MMIP is developed for high resolution, sensitivity, and accuracy at the wavelength of 265 nm. A modified polarization state analyzer is designed and applied to suppress stray light for nice polarization images, and the errors of the measured Mueller matrices are calibrated to lower than 0.007 in pixel level. The finer performance of the UV-MMIP is demonstrated by the measurements of unstained cervical intraepithelial neoplasia (CIN) specimens. The contrasts of depolarization images obtained by the UV-MMIP are dramatically improved over those obtained by our previous VIS-MMIP at the wavelength of 650 nm. A distinct evolution of depolarization in normal cervical epithelium tissue, CIN-I, CIN-II, and CIN-III specimens can be observed by the UV-MMIP with mean depolarization promotion by up to 20 times. This evolution could provide important evidence for CIN staging but can hardly be distinguished by the VIS-MMIP. The results prove that the UV-MMIP could be an effective tool in polarimetric applications with higher sensitivity.

Efficient acquisition of Mueller matrix via spatially modulated polarimetry at low light field.

Mueller polarimetry performed in low light field with high speed and accuracy is important for the diagnosis of living biological tissues. However, efficient acquisition of the Mueller matrix at low light field is challenging owing to the interference of background-noise. In this study, a spatially modulated Mueller polarimeter (SMMP) induced by a zero-order vortex quarter wave retarder is first presented to acquire the Mueller matrix rapidly using only four camera shots rather than 16 shots, as in the state of the art technique. In addition, a momentum gradient ascent algorithm is proposed to accelerate the reconstruction of the Mueller matrix. Subsequently, a novel adaptive hard thresholding filter combined with the spatial distribution characteristics of photons at different low light levels, in addition to a low-pass fast-Fourier-transform filter, is utilized to remove redundant background noise from raw-low intensity distributions. The experimental results illustrate that the proposed method is more robust to noise perturbation, and its precision is almost an order of magnitude higher than that of the classical dual-rotating retarder Mueller polarimetry at low light field.

Highly Stereoselective Diels-Alder Reactions Catalyzed by Diboronate Complexes.

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond.

Design of an extreme ultraviolet lithography projection objective with a grouping design method through forward and reverse real ray tracing.

As the logic node gets more and more advanced, the performance of extreme ultraviolet (EUV) objective projection is required to be higher and higher in a large field of view. It is known that a good initial structure can greatly reduce the dependence on the experience of optical designers. In this paper, a grouping design method through forward and reverse real ray tracing is proposed to design the aspheric initial structure for the EUV objective system. The system is first divided into three groups, and each spherical group is designed separately. Then, the three groups are connected as a whole spherical initial objective system. Through forward and reverse real ray tracing, each spherical group is recalculated to an aspheric structure in turn. Finally, an iterative process is applied to improve the performance of the aspheric initial structure. The aspheric initial structure calculated by this method can be taken as a good starting point for further optimization. As verification of the design method, a six-aspheric-mirror EUV lithography objective with a numerical aperture of 0.33 has been designed, whose root mean square (RMS) wavefront error is less than 0.2 nm and distortion is less than 0.1 nm.

Glutathione Is Involved in the Reduction of Methylarsenate to Generate Antibiotic Methylarsenite in Enterobacter sp. Strain CZ-1.

Methylarsenate (MAs(V)) is a product of microbial arsenic (As) biomethylation and has also been widely used as an herbicide. Some microbes are able to reduce nontoxic MAs(V) to highly toxic methylarsenite (MAs(III)) possibly as an antibiotic. The mechanism of MAs(V) reduction in microbes has not been elucidated. Here, we found that the bacterium Enterobacter sp. CZ-1 isolated from an As-contaminated paddy soil has a strong ability to reduce MAs(V) to MAs(III). Using a MAs(III)-responsive biosensor to detect MAs(V) reduction in E. coli Trans5α transformants of a genomic library of Enterobacter sp. CZ-1, we identified gshA, encoding a glutamate-cysteine ligase, as a key gene involved in MAs(V) reduction. Heterologous expression of gshA increased the biosynthesis of glutathione (GSH) and MAs(V) reduction in E. coli Trans5α. Deletion of gshA in Enterobacter sp. CZ-1 abolished its ability to synthesize GSH and decreased its MAs(V) reduction ability markedly, which could be restored by supplementation of exogenous GSH. In the presence of MAs(V), Enterobacter sp. CZ-1 was able to inhibit the growth of Bacillus subtilis 168; this ability was lost in the gshA-deleted mutant. In addition, deletion of gshA greatly decreased the reduction of arsenate to arsenite. These results indicate that GSH plays an important role in MAs(V) reduction to generate MAs(III) as an antibiotic. IMPORTANCE Arsenic is a ubiquitous environmental toxin. Some microbes detoxify inorganic arsenic through biomethylation, generating relatively nontoxic pentavalent methylated arsenicals, such as methylarsenate. Methylarsenate has also been widely used as an herbicide. Surprisingly, some microbes reduce methylarsenate to highly toxic methylarsenite possibly to use the latter as an antibiotic. How microbes reduce methylarsenate to methylarsenite is unknown. Here, we show that gshA encoding a glutamate-cysteine ligase in the glutathione biosynthesis pathway is involved in methylarsenate reduction in Enterobacter sp. CZ-1. Our study provides new insights into the crucial role of glutathione in the transformation of a common arsenic compound to a natural antibiotic.

Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice.

(-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 µM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.

Holistic and efficient calibration method for Mueller matrix imaging polarimeter with a high numerical aperture.

High-numerical aperture (N A>0.6) Mueller matrix imaging polarimeter (MMIP) (high-NA MMIP) is urgently needed for higher resolution. Usually, the working distance of high-NA MMIP is too short to perform in situ calibration by a usual reference sample, such as polarizer and retarder plates. The polarization effects of the substrate that attach the sample are never calibrated. So, the resolution and accuracy of the MMIP is hard to further promote. In this paper, a holistic and efficient calibration method is innovated for high-NA MMIP. Two film polarizers and a film retarder as well as a blank substrate are first adopted as the reference samples in calibration. Different from the conventional eigenvalue calibration method (ECM), the holistic calibration theory and process are established. All polarimetric errors arising from the devices, subsystems, and the substrate can be calibrated in one process. The normalized measurement error is less than 0.0024 for NA 0.95 MMIP, which is an order of magnitude lower than those of NA 0.1 and 0.2 MMIPs in publications. The excellent performance of calibrated high-NA MMIP is demonstrated by tissue polarimetry with higher resolution, accuracy, and more appropriate dynamic range.

Demethylation of the Antibiotic Methylarsenite is Coupled to Denitrification in Anoxic Paddy Soil.

Arsenic (As) biomethylation is an important component of the As biogeochemical cycle, which produces methylarsenite [MAs(III)] as an intermediate product. Its high toxicity is used by some microbes as an antibiotic to kill off other microbes and gain a competitive advantage. Some aerobic microbes have evolved a detoxification mechanism to demethylate MAs(III) via the dioxygenase C-As lyase ArsI. How MAs(III) is demethylated under anoxic conditions is unclear. We found that nitrate addition to a flooded paddy soil enhanced MAs(III) demethylation. A facultative anaerobe Bacillus sp. CZDM1 isolated from the soil was able to demethylate MAs(III) under anoxic nitrate-reducing conditions. A putative C-As lyase gene (BcarsI) was identified in the genome of strain CZDM1. The expression of BcarsI in the As-sensitive Escherichia coli AW3110 conferred the bacterium the ability to demethylate MAs(III) under anoxic nitrate-reducing condition and enhanced its resistance to MAs(III). Both Bacillus sp. CZDM1 and E. coli AW3110 harboring BcarsI could not demethylate MAs(III) under fermentative conditions. Five conserved amino acid resides of cysteine, histidine, and glutamic acid are essential for MAs(III) demethylation under anoxic nitrate-reducing conditions. Putative arsI genes are widely present in denitrifying bacteria, with 75% of the sequenced genomes containing arsI, also possessing dissimilatory nitrate reductase genes narG or napA. These results reveal a novel mechanism in which MAs(III) is demethylated via ArsI by coupling to denitrification, and such a mechanism is likely to be common in an anoxic environment such as paddy soils and wetlands.

Total Syntheses of Vicinal Dichloride Monoterpenes Enabled by Aza-Bellus-Claisen Rearrangement.

Diastereoselective syntheses of syn- and anti-vicinal dihalides were achieved via an aza-Bellus-Claisen rearrangement, which involved the reaction of an α-chloro carboxylic acid chloride with halogen-substituted trans-allyl morpholines in the presence of Lewis acids. The developed method was used for the total synthesis of a group of monoterpene natural products bearing vicinal dichloride subunits.

Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of ß-Lactones.

The collective synthesis of skeletally diverse Stemona alkaloids featuring tailored dyotropic rearrangements of ß-lactones as key elements is described. Specifically, three typical 5/7/5 tricyclic skeletons associated with stemoamide, tuberostemospiroline and parvistemonine were first accessed through chemoselective dyotropic rearrangements of ß-lactones involving alkyl, hydrogen, and aryl migration, respectively. By the rational manipulation of substrate structures and reaction conditions, these dyotropic rearrangements proceeded with excellent efficiency, good chemoselectivity and high stereospecificity. Furthermore, several polycyclic Stemona alkaloids, including saxorumamide, isosaxorumamide, stemonine and bisdehydroneostemoninine, were obtained from the aforementioned tricyclic skeletons through late-stage derivatizations. A novel visible-light photoredox-catalyzed formal [3+2] cycloaddition was also developed, which offers a valuable tool for accessing oxaspirobutenolide and related scaffolds.

Stereoselective Synthesis of Cyclohepta[b]indoles by Visible-Light-Induced [2+2]-Cycloaddition/retro-Mannich-type Reactions.

A novel method for the concise synthesis of cyclohepta[b]indoles in high yields was developed. The method involves a visible-light-induced, photocatalyzed [2+2]-cycloaddition/ retro-Mannich-type reaction of enaminones. Experimental and computational studies suggested that the reaction is a photoredox process initiated by single-electron oxidation of an enaminone moiety, which undergoes subsequent cyclobutane formation and rapidly fragmentation in a radical-cation state to form cyclohepta[b]indoles.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A.

A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13(R)-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 2: The Final Phase and Completion.

The final phase of the total synthesis of (-)-spirochensilide A is described. A tungsten-mediated cyclopropene-based Pauson-Khand reaction was developed to form the spiral CD ring system with desired stereochemistry at the C13 quaternary center. Other important steps enabling completion of this synthesis included an intermolecular aldol condensation to link the ABCD core with the EF fragment and a Cu-mediated 1,4-addition to stereoselectively install the C21 stereogenic center. The chemistry developed for this total synthesis of (-)-spirochensilide A (1) will aid the synthesis of polycyclic natural products bearing this unique spiral ring system.

Strain-Driven Dyotropic Rearrangement: A Unified Ring-Expansion Approach to α-Methylene-γ-butyrolactones.

An unprecedented strain-driven dyotropic rearrangement of α-methylene-ß-lactones has been realized, which enables the efficient access of a wide range of α-methylene-γ-butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL-containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.