Joint Exposure to Ambient Air Pollutants, Genetic Risk, and Ischemic Stroke: A Prospective Analysis in UK Biobank.

BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.

Enantioselective [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Vinylazaarenes through Asymmetric Photoredox Catalysis.

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses a variety of vinylazaarenes as partners and is catalyzed by a polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid as a bifunctional chiral photosensitizer. A wide array of pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, and diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/ß-substituted vinylazaarenes are compatible with such an unprecedented photoredox catalytic pathway, resulting in the successful assembly of an all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on the product.

In-cell Catalysis by Tethered Organo-Osmium Complexes Generates Selectivity for Breast Cancer Cells.

Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi-targeting strategy to overcome drug resistance. Nonetheless, many in-cell catalysts in development are hindered by deactivation by endogenous nucleophiles. We have synthesised a highly potent, stable Os-based 16-electron half-sandwich ('piano stool') catalyst by introducing a permanent covalent tether between the arene and chelated diamine ligand. This catalyst exhibits antiproliferative activity comparable to the clinical drug cisplatin towards triple-negative breast cancer cells and can overcome tamoxifen resistance. Speciation experiments revealed Os to be almost exclusively albumin-bound in the extracellular medium, while cellular accumulation studies identified an energy-dependent, protein-mediated Os accumulation pathway, consistent with albumin-mediated uptake. Importantly, the tethered Os complex was active for in-cell transfer hydrogenation catalysis, initiated by co-administration of a non-toxic dose of sodium formate as a source of hydride, indicating that the Os catalyst is delivered to the cytosol of cancer cells intact. The mechanism of action involves the generation of reactive oxygen species (ROS), thus exploiting the inherent redox vulnerability of cancer cells, accompanied by selectivity for cancerous cells over non-tumorigenic cells.

A highly sensitive fluorescence biosensor for aflatoxins B1 detection based on polydiacetylene liposomes combined with exonuclease III-assisted recycling amplification.

A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.

Enantioselective Chemodivergent Three-Component Radical Tandem Reactions through Asymmetric Photoredox Catalysis.

Chemodivergent synthesis has been achieved in asymmetric photocatalysis. Under a dual catalyst system consisting of a chiral phosphoric acid and DPZ as a photosensitizer, different inorganic bases enabled the formation of two sets of valuable products from the three-component radical tandem transformations of 2-bromo-1-arylenthan-1-ones, styrenes, and quinoxalin-2(1H)-ones. The key to success was the distinct pKa environment, in which the radicals that formed on the quinoxalin-2(1H)-one rings after two radical addition processes underwent either single-electron oxidation or single-electron reduction. In addition, this work represents the first use of quinoxalin-2(1H)-ones in asymmetric photoredox catalysis.

Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation.

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due to the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, a higher stability of the product to the substrate. It has thus led to rather limited examples of success. Herein, we report a photoredox catalytic hydrogen atom transfer (HAT) and enantioselective protonation strategy for the challenging asymmetric olefin isomerization. As a paradigm, by establishing a dual catalyst system involving a visible light photosensitizer DPZ and a chiral phosphoric acid, with the assistance of N-hydroxyimide to perform HAT, a wide array of allylic azaarene derivatives, featuring α-tertiary carbon stereocenters and ß-C═C bonds, was synthesized with high yields, ees, and E/Z ratios starting from the conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility of assembling deuterium on stereocenters by using inexpensive D2O as a deuterium source further underscores the broad applicability and promising utility of this strategy. Moreover, mechanistic studies have provided clear insights into its challenges in terms of reactivity and enantioselectivity. The exploration will robustly inspire the development of thermodynamically unfavorable asymmetric olefin isomerizations.

scRAA: the development of a robust and automatic annotation procedure for single-cell RNA sequencing data.

A critical task in single-cell RNA sequencing (scRNA-Seq) data analysis is to identify cell types from heterogeneous tissues. While the majority of classification methods demonstrated high performance in scRNA-Seq annotation problems, a robust and accurate solution is desired to generate reliable outcomes for downstream analyses, for instance, marker genes identification, differentially expressed genes, and pathway analysis. It is hard to establish a universally good metric. Thus, a universally good classification method for all kinds of scenarios does not exist. In addition, reference and query data in cell classification are usually from different experimental batches, and failure to consider batch effects may result in misleading conclusions. To overcome this bottleneck, we propose a robust ensemble approach to classify cells and utilize a batch correction method between reference and query data. We simulated four scenarios that comprise simple to complex batch effect and account for varying cell-type proportions. We further tested our approach on both lung and pancreas data. We found improved prediction accuracy and robust performance across simulation scenarios and real data. The incorporation of batch effect correction between reference and query, and the ensemble approach improve cell-type prediction accuracy while maintaining robustness. We demonstrated these through simulated and real scRNA-Seq data.

What impacts ecosystem services in tropical coastal tourism cities? A comparative case study of Haikou and Sanya, China.

The ecological environment of tourism-oriented towns is attracting increasing attention. Taking the cities of Haikou and Sanya as examples, we examined changes in six ecosystem services (ES), including water conservation (WC), crop production (CP), soil retention (SR), carbon storage (CS), habitat quality (HQ), and tourism recreation (TR) from 2005 to 2020. From the three perspectives of geographical environment, socioeconomic development, and tourism development force, 14 indicators were chosen to examine the impact on ES. Except for Haikou's TR, the other ES of Haikou and Sanya showed a decreasing trend from 2005 to 2020. The values of six ES were lower in coastal zones than in noncoastal zones, which were more obvious in Sanya. Specifically, the areas of low value in Sanya were concentrated in the coastal region, and the areas with low value in Haikou were primarily distributed in blocks along the coast and in bands or points in the central and southern areas. From the perspective of influencing factors, the natural environmental factors dominate in Haikou, followed by the socio-economic factors and finally the tourism development factors, while the natural environmental factors also dominate in Sanya, followed by the tourism development factors and finally the socio-economic factors. We provided recommendations for sustainable tourism development in Haikou and Sanya. This study has significant implications for both integrated management and scientific decision-making to enhance the ES of tourism destinations.

Catalytic Asymmetric Hydrophosphinylation of 2-Vinylazaarenes to Access P-Chiral 2-Azaaryl-Ethylphosphine Oxides.

A chiral Brønsted acid-catalysed asymmetric hydrophosphinylation of 2-vinylazaarenes by secondary phosphine oxides is described. A variety of P-chiral 2-azaaryl-ethylphosphine oxides are synthesized with high yields and ees, of which both the substituents of phosphines and azaarenes can be flexibly modulated, underscoring an exceptionally broad scope of substrates. These adducts are valuable to asymmetric metal catalysis since the resultant P-chiral tertiary phosphines from the reduction of them are verified as a kind of effective C1 -symmetric chiral 1,5-hybrid P,N-ligands. Importantly, this catalysis platform enables the generic and efficient kinetic resolution of P-chiral secondary phosphine oxides. It thus provides an expedient approach to access the enantiomers of the P-chiral tertiary phosphine oxides derived from asymmetric hydrophosphinylation, further improving the utility of the method.

Overexpression of miR-383-3p protects cardiomyocytes against hypoxia/reoxygenation injury via regulating PTEN/PI3K/AKT signal pathway.

MicroRNAs are widely reported as biomarkers and therapeutic targets in cardiovascular diseases. This study is aimed to expound on the regulatory responsibility of miR-383-3p in H/R-induced injury of H9c2 cells. In this study, H9c2 cells were administrated with H/R. MiR-383-3p expression was measured using qRT-PCR. ELISA was used to determine lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Reactive oxygen species (ROS) were detected with 2,7-Dichlorodihydrofluorescein diacetate probe. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide, flow cytometry, and TUNEL experiments were conducted to measure cell viability and apoptosis. Cleaved caspase-3, caspase-3, Bax, Bcl-2, PTEN, PI3K, p-PI3K, Akt, p-AKT expression levels were examined by Western blot. Cleaved caspase-3 expression was also measured by immunofluorescence staining. Dual-luciferase reporter gene assay was applied to validate the binding sites in miR-383-3p and the 3'UTR of PTEN. We reported that, miR-383-3p expression in H9c2 cells treated with H/R was remarkably decreased. MiR-383-3p overexpression ameliorated oxidative stress and apoptosis and promoted cell viability in H9c2 cells treated with H/R, while miR-383-3p inhibitor showed the reverse effects. PTEN was identified as a target gene of miR-383-3p. Additionally, enhancement of PTEN expression abolished the influences of miR-383-3p on H9c2 cells. MiR-383-3p mimics could significantly decrease PTEN expression in H9c2 cells while increasing p-PI3K expression and p-AKT expression, while the miR-383-3p inhibitors showed the opposed effects. In conclusion, miR-383-3p protected H9c2 cells from H/R-induced injury via regulating PTEN/PI3K/AKT signal pathway.

Effect of acid-alkali treatment on serum protein adsorption and bacterial adhesion to porous titanium.

Modification of the titanium (Ti) surface is widely known to influence biological reactions such as protein adsorption and bacterial adhesion in vivo, ultimately controlling osseointegration. In this study, we sought to investigate the correlation of protein adsorption and bacterial adhesion with the nanoporous structure of acid-alkali-treated Ti implants, shedding light on the modification of Ti implants to promote osseointegration. We fabricated nontreated porous Ti (NTPT) by powder metallurgy and immersed it in mixed acids and NaOH to obtain acid-alkali-treated porous Ti (AAPT). Nontreated dense sample (NTDT) served as control. Our results showed that nanopores were formed after acid-alkali treatment. AAPT showed a higher specific surface area and became much more hydrophilic than NTPT and NTDT (p < 0.001). Compared to dense samples, porous samples exhibited a lower zeta potential and higher adsorbed protein level at each time point within 120 min (p < 0.001). AAPT formed a thicker protein layer by serum precoating than NTPT and NTDT (p < 0.001). The main adsorbed proteins on AAPT and NTPT were albumin, α1 antitrypsin, transferrin, apolipoprotein A1, complement C3 and haptoglobin α1 chain. The amounts of bacteria adhering to the serum-precoated samples were lower than those adhering to the nonprecoated samples (p < 0.05). Lower-molecular-weight proteins showed higher affinity to porous Ti. In conclusion, acid-alkali treatment facilitated protein adsorption by porous Ti, and the protein coating tended to prevent bacteria from adhering. These findings may be utilized for Ti implant modification aimed at reducing bacterial adhesion and enhancing osseointegration. Graphical abstract.

Comparative Transcriptome Analysis of CCCH Family in Roles of Flower Opening and Abiotic Stress in Osmanthus fragrans.

CCCH is a zinc finger family with a typical CCCH-type motif which performs a variety of roles in plant growth and development and responses to environmental stressors. However, the information about this family has not been reported for Osmanthus fragrans. In this study, a total of 66 CCCH predicted genes were identified from the O. fragrans genome, the majority of which had multiple CCCH motifs. The 66 OfCCCHs were found to be unevenly distributed on 21 chromosomes and were clustered into nine groups based on their phylogenetic analysis. In each group, the gene structure and domain makeup were comparatively conserved. The expression profiles of the OfCCCH genes were examined in various tissues, the flower-opening processes, and under various abiotic stresses using transcriptome sequencing and qRT-PCR (quantitative real-time PCR). The results demonstrated the widespread expression of OfCCCHs in various tissues, the differential expression of 22 OfCCCHs during flower-opening stages, and the identification of 4, 5, and 13 OfCCCHs after ABA, salt, and drought stress treatment, respectively. Furthermore, characterization of the representative OfCCCHs (OfCCCH8, 23, 27, and 36) revealed that they were all localized in the nucleus and that the majority of them had transcriptional activation in the yeast system. Our research offers the first thorough examination of the OfCCCH family and lays the groundwork for future investigations regarding the functions of CCCH genes in O. fragrans.

Chemical Constituent Analysis of Ranunculus sceleratus L. Using Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Ranunculus sceleratus L.(RS) has shown various pharmacological effects in traditional Chinese medicine. In our previous study, the positive therapeutic effect on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats was obtained using TianJiu treatment with fresh RS. However, the chemical profile of RS has not been clearly clarified, which impedes the research progress on the therapeutic effect of RS. Herein, an ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed to rapidly separate and identify multiple constituents in the 80% methanol extract of RS. A total of sixty-nine compounds (19 flavonoids, 22 organic acids, 6 coumarins, 4 lignans, 14 nitrogenous compounds, and 4 anthraquinones) were successfully characterized. A total of 12 of these compounds were unambiguously identified by standard samples. Their mass spectrometric fragmentation pathways were investigated. It is worth noting that flavonoids and lignans were identified for the first time in RS. In this study, we successfully provide the first comprehensive report on identifying major chemical constituents in RS by UHPLC-Q-Orbitrap HRMS. The obtained results enrich the RS chemical profile, paving the way for further phytochemical study, quality control, and pharmacological investigation of RS.

Asymmetric Hydroaminoalkylation of Alkenylazaarenes via Cooperative Photoredox and Chiral Hydrogen-Bonding Catalysis.

Chiral hydrogen-bonding (H-bonding) catalytic asymmetric conjugate addition to activated olefins has been widely used to access enantioenriched molecules containing stereocenters at the ß-position of the olefin activating groups. Herein, we report the first highly enantioselective radical-based manifold. Under a dual organocatalyst system involving a chiral phosphoric acid and DPZ as the photoredox sensitizer, transformations of N-arylglycines, in which aryls with CF3 substituents are introduced, with alkenyl azaarenes afforded valuable hydroaminoalkylation adducts with satisfactory results. In addition to the diversity of azaarenes, the method can be used to construct aryl-, alkyl- and silyl-substituted stereocenter. Control experiments and density functional theory calculations were performed to elucidate a plausible reaction mechanism and the origin of stereoselectivity, wherein nonclassical H-bonding interactions were found to assist chiral catalysts in offering sufficient enantiocontrol.

Deracemization through Sequential Photoredox-Neutral and Chiral Brønsted Acid Catalysis.

Catalytic deracemization is an ideal synthetic strategy due to its formally perfect atom utilization. Asymmetric photocatalysis has been appreciated as a promising tool to accomplish this attractive reaction pattern in an economical fashion, but it remains underdeveloped. Here, we report a new platform based on photoredox-neutral catalysis, allowing efficient and modular optical enrichment of α-amino esters and other valuable analogues. Two single-electron transfer processes between the photocatalyst and the substrates serve to provide the key prochiral intermediates, and the chiral Brønsted acid catalyst mediates enantioselective protonation to reconstitute a stereogenic C-H bond. The efficiency of deracemization is determined by the enantiofacial differentiation effect during the stereocentre-forming step.

Catalytic Reductive Cross Coupling and Enantioselective Protonation of Olefins to Construct Remote Stereocenters for Azaarenes.

A novel enantioselective protonation protocol that is triggered by reductive cross coupling of olefins is reported. When under cooperative photoredox and chiral hydrogen-bonding catalytic conditions and using a terminal reductant, various α-branched vinylketones with diverse vinylazaarenes could provide important enantioenriched azaarene derivatives containing tertiary stereocenters at their remote δ-position with high yields and enantioselectivities. This reaction system is also suitable for α-branched vinylazaarenes, thus successfully assembling elusive 1,4-stereocenters. The convenient late-stage modifications of products, especially the formation of remote ε-tertiary and ε-heteroquaternary carbon stereocenters, further highlight the important synthetic value of this method. Control experiments and density functional theory (DFT) calculations were conducted to elucidate the plausible reaction mechanism and origins of regioselectivity and stereoselectivity.

Jet quenching and medium response in high-energy heavy-ion collisions: a review.

Jet quenching has been used successfully as a hard probe to study properties of the quark-gluon plasma (QGP) in high-energy heavy-ion collisions at both the relativistic heavy-ion collider and the large hadron collider. We will review recent progresses in theoretical and phenomenological studies of jet quenching with jet transport models. Special emphasis is given to effects of jet-induced medium response on a wide variety of experimental observables and their implications on extracting transport properties of the QGP in heavy-ion collisions.

Decline in executive function in patients with white matter hyperintensities from the static and dynamic perspectives of amplitude of low-frequency fluctuations.

Cognitive impairments are characteristics of patients with white matter hyperintensities (WMHs), and hypoperfusion is currently a relatively recognized mechanism of WMHs. Brain activity is closely coupled to the regulation of local blood flow. This study aimed to investigate the abnormal local brain activity of patients with WMHs from the viewpoint of the static amplitude of low-frequency fluctuations (sALFF) and dynamic amplitude of low-frequency fluctuations (dALFF). Seventy-four patients with WMHs and 35 healthy controls (HCs) were included. Based on the Fazekas scale, patients with WMHs were further divided into a mild WMH group (n = 33, Fazekas score 1-2) and moderate-severe WMH group (n = 41, Fazekas score 3-6). The sALFF and dALFF values were calculated separately and neuropsychological tests including the Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), and Boston Naming Test (BNT) were completed by all participants. Patients with WMHs showed increased sALFF and dALFF values in the bilateral thalamus and decreased performance in the MoCA test, AVLT-immediate, AVLT-delay, AVLT-recognition, TMT-A, and BNT. The dALFF values in the bilateral thalamus was correlated with the MoCA in HCs. The sALFF values in the bilateral thalamus correlated with TMT-B in patients with WMHs. Patients with WMHs showed abnormal brain activity and decreased functional stability of the bilateral thalamus, which may be a potential mechanism of decreased executive function.

Silver-Catalyzed Activation of Terminal Alkynes for Synthesizing Nitrogen-Containing Molecules.

Alkynes are one of the most abundant chemicals in organic chemistry, and therefore the development of catalytic reactions to transform alkynes into other useful functionalities is of great value. In recent decades, extraordinary advances have been made in this area with transition-metal catalysis, and silver-based reagents are ideal for the activation of alkynes. This high reactivity is probably due to the superior π-Lewis acidic, carbophilic behavior of silver(I), allowing it to selectively activate carbon-carbon triple bonds (C≡C) through the formation of a silver-π complex. Within this field, we have been interested in the activation and subsequent reactions of readily accessible terminal alkynes for the synthesis of nitrogen-containing compounds, which has generally received less attention than methods involving internal alkynes. This is possibly due to the lack of suitable reactive reaction partners that are compatible under transition metals. Therefore, a thorough understanding of the factors that influence homogeneous silver catalysis and the identification of the appropriate reaction partners can provide a powerful platform for designing more efficient silver-catalyzed reactions of terminal alkynes. In this context, we envisioned that using readily available, environmentally benign, and inexpensive trimethylsilyl azide (TMSN3) or an isocyanide as the nitrogen-donor would be the key to develop novel reactions of terminal alkynes.This Account describes our efforts since 2013 toward the development of novel silver-catalyzed tandem reactions of terminal alkynes with either TMSN3 or isocyanides for the assembly of various nitrogen-containing compounds. The first section of this Account discusses the initial developments in the silver-catalyzed hydroazidation of terminal alkynes with TMSN3 and the subsequent advances made in our laboratory. We first describe the discovery and experimental and computational mechanistic investigations of silver-catalyzed hydroazidation reactions, which is the most efficient strategy reported to date for accessing vinyl azides. Mechanistic study of this hydroazidation reaction provides an alternative activation mode for terminal alkyne conversion in transition metal catalysis. We then present the chemistry of in situ generated vinyl azides, including one-pot tandem radical addition/cyclization or migration reactions of terminal alkynes to access a variety of nitrogen-containing molecules. Finally, we discuss the one-pot, multistep tandem hydroazidation and 1,2-azide migratory gem-difluorination of terminal alkynes for the synthesis of ß-difluorinated alkyl azides. The second section describes the silver-catalyzed coupling reactions between terminal alkynes and isocyanides, which offer a straightforward method for accessing synthetically useful building blocks, such as pyrroles, allenamides, benzofuran, vinyl sulfones, indazolines, propiolonitriles, and pyrazoles. The high efficiency, mild conditions, low cost, broad substrate scope, high chemo- and regioselectivity, step economy, and ecofriendliness of the developed approaches make them attractive and practical. The progress in this area provides guiding principles for designing new reactions of terminal alkynes that can be extended to various nitrogen-containing molecules of interest to medicinal and materials chemists.

Cladding softened fiber for sensitivity enhancement of distributed acoustic sensing.

Fiber-optic distributed acoustic sensing (DAS) technology with high spatial and strain resolutions has been widely used in many practical applications. New methods to enhance the phase sensitivity of sensing fiber are worth exploring to further improve DAS performances, although the standard single-mode fiber (SSMF) has been widely used for DAS technology. In this work, we propose and demonstrate the concept of enhancing the phase sensitivity of DAS by softening the cladding of the sensing fiber, for the first time. The theoretical analysis indicates that softening sensing fiber cladding is an effective way to improve phase sensitivity. Thus, we fabricated cladding softened fibers (CSFs) and tested their phase sensitivities experimentally. According to the results, it is found that the phase sensitivity of the CSF with 0.48 WT% phosphorus-doping concentration and 80 µm cladding diameter is 22% and 54% higher than that of the non-phosphorus-doping fiber with 80 µm cladding diameter and SSMF, respectively. The results show that by reducing fiber cladding Young's modulus with higher phosphorus-doping concentration, the DAS phase sensitivity can be enhanced effectively, verifying the theoretical analysis. Also, we found that the phase sensitivity enhancement of the sensing fiber has a linear relationship with the cladding phosphorus-doping concentration, i.e. Young's modulus. In conclusion, the reported CSF paves a way for improving the DAS phase sensitivity and would be applied to other major optical fiber sensing systems as a better sensing element over SSMF due to the enhancement in the elasto-optical effect of the sensing fiber.