A chondroitin sulphate hydrogel with sustained release of SDF-1α for extensive cartilage defect repair through induction of cell homing and promotion of chondrogenesis.

Articular cartilage damage represents a prevalent clinical disease in orthopedics, with its regeneration and repair constituting a central focus in ongoing research endeavors. While hydrogel technology has achieved notable progress in the field of cartilage regeneration, addressing the repair of larger cartilage defects remains a significant and formidable challenge. In pursuit of achieving the repair of extensive cartilage defects, this study designed a polydopamine-modified chondroitin sulfate hydrogel loaded with SDF-1α (P-SCMA). This hydrogel, capable of directly providing glycosaminoglycans (GAGs), served as a platform for carrying growth factors and attracting mesenchymal stem cells for the in situ reconstruction of extensive cartilage defects. The results indicate that the P-SCMA hydrogel is capable of not only directly providing GAGs but also sustainably releasing SDF-1α. In the early stages, it promotes cell adhesion and proliferation and induces cell homing, while in the later stages, it further induces chondrogenesis by inhibiting the Wnt/ß-catenin pathway. This bioactive hydrogel, which possesses the functions of providing GAGs, promoting cell proliferation, inducing cell homing and chondrogenesis, is capable of promoting cartilage repair in multiple ways, providing new perspectives for the repair of extensive cartilage defects.

A novel cathode interphase formation methodology by preferential adsorption of a borate-based electrolyte additive.

The coupling of high-capacity cathodes and lithium metal anodes promises to be the next generation of high-energy-density batteries. However, the fast-structural degradations of the cathode and anode challenge their practical application. Herein, we synthesize an electrolyte additive, tris(2,2,3,3,3-pentafluoropropyl) borane (TPFPB), for ultra-stable lithium (Li) metal||Ni-rich layered oxide batteries. It can be preferentially adsorbed on the cathode surface to form a stable (B and F)-rich cathode electrolyte interface film, which greatly suppresses the electrolyte-cathode side reactions and improves the stability of the cathode. In addition, the electrophilicity of B atoms in TPFPB enhances the solubility of LiNO3 by 30 times in ester electrolyte to significantly improve the stability of the Li metal anode. Thus, the Li||Ni-rich layered oxide full batteries using TPFPB show high stability and an ultralong cycle life (up to 1500 cycles), which also present excellent performance even under high voltage (4.8 V), high areal mass loading (30 mg cm-2) and wide temperature range (-30∼60°C). The Li||LiNi0.9Co0.05Mn0.05O2 (NCM90) pouch cell using TPFPB with a capacity of 3.1 Ah reaches a high energy density of 420 Wh kg-1 at 0.1 C and presents outstanding cycling performance.

Electron Transporting Polymeric Materials with Partial Quaternization for High-Performance Organic Solar Cells.

Efficient cathode interfacial layers (CILs) have become a crucial component of organic solar cells (OSCs). Charge extraction barriers, interfacial trap states, and significant transport resistance may be induced due to the unfavorable cathode interlayer, limiting the device performance. In this study, poly(4-vinylpyridine) is used as the CIL for OSCs, and a new type of CIL named P4VP-I is synthesized through the quaternization strategy. Compared to P4VP, P4VP-I CIL exhibits enhanced conductivity and optimized work function. OSCs employing the P4VP-I ETL demonstrate prolonged carrier lifetime, suppressed charge recombination, and achieve higher power conversion efficiencies (PCE) than the commonly used ETLs such as PFN-Br and Phen-NaDPO.

Discovery of a Highly Promising Disulfide Derivative Scaffold as Inhibitor of SARS-CoV-2 main protease.

The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor  is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1a-h), dithiocarbamate-Cu(II) complexes (2a-hCu) and disulfide derivatives (2a-e, 2i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7 and 15.1-111 µM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1g may be a partial reversible inhibitor, while 2d and 2f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2d, 2f-Cu and 1g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2f-Cu and 2d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2d and 1g exhibit low cytotoxicity, whereas 2f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.

Astragaloside IV promotes the pyroptosis of airway smooth muscle cells in childhood asthma by suppressing HMGB1/RAGE axis to inactivate NF-κb pathway.

Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from Astragalus membranaceus, which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 µM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, in vivo experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.

Characterization of WO3/Silicone Rubber Composites for Hydrogen-Sensitive Gasochromic Application.

WO3 and silicone rubber (SR)-based gasochromic composites were fabricated to detect hydrogen leaks at room temperature. WO3 rod-like nanostructures were uniformly distributed in the SR matrix, with a particle size of 60-100 nm. The hydrogen permeability of these composites reached 1.77 cm3·cm/cm2·s·cmHg. At a 10% hydrogen concentration, the visible light reflectance of the composite decreased 49% during about 40 s, with a color change rate of 6.4% s-1. Moreover, the composite detected hydrogen concentrations as low as 0.1%. And a color scale was obtained for easily assessing hydrogen concentrations in the environment based on the color of composites. Finally, the composite materials as disposable sensors underwent testing at several Sinopec hydrogen refueling stations.

Unlocking the potential of stimuli-responsive biomaterials for bone regeneration.

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

A nanoplatform based on allylthiopurine bio-MOF and glycosylated AIE PARP inhibitor for cancer synthetic lethal therapy.

A biological nanoplatform (Gal-ANI@ZnAP NPs) was constructed based on a prodrug-skeletal metal-organic framework (MOF) using purine nucleobase analogue prodrug 6-allylthiopurine as a bioactive ligand, and functionalized with AIE fluorescent PARP inhibitor glycoconjugate for visualization therapy and synthetic lethal cancer therapy. This nanoplatform could actively target cancer cells, selectively release drugs in response to esterase/pH, and visualize drug uptake. In vitro studies revealed that Gal-ANI@ZnAP NPs increased the synthetic lethality in cancer cells by inducing DNA repair failure with the simultaneous targeting of PARP and nucleotide metabolism, thereby exhibiting a significant cancer-killing effect. The study presents a novel strategy to construct an AIE nanoplatform using pharmaceutical molecules for drug uptake visualization and boosting synthetic lethality in cancer.

Molecular Characterization and Expression Analysis of a Gene Encoding 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGR) from Bipolaris eleusines, an Ophiobolin A-Producing Fungus.

Ophibolin A, a fungal sesterterpene, exerts a pivotal influence in a diverse array of biological processes, encompassing herbicidal, bactericidal, fungicidal, and cytotoxic activities. Sixty genes associated with sesterterpene compound biosynthesis were obtained from Bipolaris eleusines via transcriptome sequencing, and those closely linked to ophiobolin A biosynthesis were subsequently filtered. A gene encoding 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) that catalyzes the first committed step of ophiobolin biosynthesis in the mevalonic acid (MVA) pathway was isolated and characterized using RACE (Rapid Amplification of cDNA Ends) technology from ophiobolin A-producing fungus, B. eleusines. The full-length cDNA of the B. eleusines HMGR gene (BeHMGR) was 3906 bp and contained a 3474 bp open reading frame (ORF) encoding 1157 amino acids. Sequence analysis revealed that deduced BeHMGR had high homology to the known HMGRs from Pyrenophora tritici-repentis and Leptosphaeria maculans. It had a calculated molecular mass of about 124.65 kDa and an isoelectric point (pI) of 6.90. It contained two putative HMG-CoA-binding motifs and two NADP(H)-binding motifs. Induced expression analysis of the BeHMGR gene by methyl jasmonate treatment using quantitative fluorescence PCR showed that it significantly elevated after 3 h of methyl jasmonate treatment, peaked at 6 h, and then gradually decreased. This demonstrates that BeHMGR gene expression is induced by methyl jasmonate.

A dual RNA-seq analyses revealed dynamic arms race during the invasion of walnut by Colletotrichum gloeosporioides.

BACKGROUND: Walnut anthracnose caused by Colletotrichum gloeosporioides seriously endangers the yield and quality of walnut, and has now become a catastrophic disease in the walnut industry. Therefore, understanding both pathogen invasion mechanisms and host response processes is crucial to defense against C. gloeosporioides infection. RESULTS: Here, we investigated the mechanisms of interaction between walnut fruits (anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts) and C. gloeosporioides at three infection time points (24hpi, 48hpi, and 72hpi) using a high-resolution time series dual transcriptomic analysis, characterizing the arms race between walnut and C. gloeosporioides. A total of 20,780 and 6670 differentially expressed genes (DEGs) were identified in walnut and C. gloeosporioides against 24hpi, respectively. Generous DEGs in walnut exhibited opposite expression patterns between F26 and F423, which indicated that different resistant materials exhibited different transcriptional responses to C. gloeosporioides during the infection process. KEGG functional enrichment analysis indicated that F26 displayed a broader response to C. gloeosporioides than F423. Meanwhile, the functional analysis of the C. gloeosporioides transcriptome was conducted and found that PHI, SignalP, CAZy, TCDB genes, the Fungal Zn (2)-Cys (6) binuclear cluster domain (PF00172.19) and the Cytochrome P450 (PF00067.23) were largely prominent in F26 fruit. These results suggested that C. gloeosporioides secreted some type of effector proteins in walnut fruit and appeared a different behavior based on the developmental stage of the walnut. CONCLUSIONS: Our present results shed light on the arms race process by which C. gloeosporioides attacked host and walnut against pathogen infection, laying the foundation for the green prevention of walnut anthracnose.

Differential carbon accumulation of microbial necromass and plant lignin by pollution of polyethylene and polylactic acid microplastics in soil.

The wide microplastics (MPs) occurrence affects soil physicochemical and biological properties, thereby influencing its carbon cycling and storage. However, the regulation effect of MPs on soil organic carbon (SOC) formation and stabilization remains unclear, hindering the accurate prediction of carbon sequestration in future global changes under continuous MP pollution. Phospholipid fatty acids, amino sugars and lignin phenols were used in this study as biomarkers for microbial community composition, microbial necromass and plant lignin components, respectively, and their responses to conventional (polyethylene; PE) and biodegradable (polylactic acid; PLA) MPs were explored. Results showed PLA MPs had positive effects on soil microbial biomass, while the positive and negative effects of PE MPs on microbial biomass varied with MP concentration. PE and PLA MPs increased microbial necromass contents and their contribution to SOC, mainly due to the increase in fungal necromass. On the contrary, PE and PLA MPs reduced lignin phenols and their contribution to SOC, mainly owing to the reduction in vanillyl-type phenols. The response of microbial necromass to PLA MPs was higher than that to PE MPs, whereas the response of lignin phenols was the opposite. MPs increased SOC level, with 83%-200% and 50%-75% of additional SOC in PE and PLA treatments, respectively, originating from microbial necromass carbon. This finding indicates that the increase in SOC pool in the presence of MPs can be attributed to soil microbial necromass carbon, and MPs increased capacity and efficacy of microbial carbon pump by increasing microbial turnover and reducing microbial N limitation. Moreover, the increase in amino sugars to lignin phenols ratio in PE treatment was higher than that in PLA treatment, and the increase in SOC content in PLA treatment was higher than that in PE treatment, indicating a high possibility of SOC storage owing to PLA MPs.

Baicalin protects against hepatocyte injury caused by aflatoxin B1 via the TP53-related ferroptosis Pathway.

OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.

Acupuncture modulation of the ACE/Ang II/AT1R and ACE2/Ang(1-7)/MasR pathways in the rostral ventrolateral medulla reduces sympathetic output and prevents cardiac injury caused by SHR hypertension.

Acupuncture can reduce blood pressure, heart rate (HR), and ameliorate cardiac damage by modulating the excitability of the sympathetic nervous system, but the exact mechanism of this effect remains unclear. This study investigated the potential mechanisms of acupuncture in the treatment of cardiac damage in hypertension. Spontaneously hypertensive rats (SHR) were used as the hypertension model with Wistar-Kyoto rats as the control. Manual acupuncture, electroacupuncture, and metoprolol were used as interventions. Systolic and diastolic blood pressure (SBP, DBP) plus HR were monitored with cardiac structure determined using Masson staining. Angiotensin II (Ang II) and norepinephrine in myocardium were detected with ELISA as was Ang(1-7) and gamma aminobutyric acid (GABA) in the rostral ventrolateral medulla (RVLM). Expression of mRNA for collagen type I (Col-I), Col-III, actin α1 (ACTA1), and thrombospondin 4 (THBS4) in myocardium was detected using real-time PCR. Expression of angiotensin converting enzyme (ACE), Ang II, angiotensin II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) proteins in RVLM was monitored using western blot. After manual acupuncture and electroacupuncture treatment, SHRs showed decreased SBP, DBP and HR, reduced myocardial damage. There was decreased expression of the ACE/Ang II/AT1R axis, and increased expression of the ACE2/Ang(1-7)/MasR axis within the RVLM. GABA levels were increased within the RVLM and norepinephrine levels were decreased in myocardial tissue. Metoprolol was more effective than either manual acupuncture or electroacupuncture. Acupuncture directed against hypertensive cardiac damage may be associated with regulation of ACE/Ang II/AT1R and the ACE2/Ang(1-7)/MasR pathway within the RLVM to reduce cardiac sympathetic excitability.

Automated cardiac vortex ring identification and characterization based on Recurrent All-Pairs Field Transforms and Lagrangian Averaged Vorticity Deviation.

Automated identification of cardiac vortices is a formidable task due to the complex nature of blood flow within the heart chambers. This study proposes a novel approach that algorithmically characterizes the identification criteria of these cardiac vortices based on Lagrangian Averaged Vorticity Deviation (LAVD). For this purpose, the Recurrent All-Pairs Field Transforms (RAFT) is employed to assess the optical flow over the Phase Contrast Magnetic Resonance Imaging (PC-MRI), and to construct a continuous blood flow velocity field and reduce errors that arise from the integral process of LAVD. Additionally, Generalized Hough Transform (GHT) is applied for automated depiction of the structure of cardiac vortices. The effectiveness of this method is demonstrated and validated by the computation of the acquired cardiac flow data. The results of this comprehensive visual and analytical study show that the evolution of cardiac vortices can be effectively described and displayed, and the RAFT framework for optical flow can synthesize the in-between PC-MRIs with high accuracy. This allows cardiologists to acquire a deeper understanding of intracardiac hemodynamics and its impact on cardiac functional performance.

Benefits of adjuvant chemotherapy in elderly patients with stage IB-IIIB non-small cell lung cancer: a propensity-matched analysis.

Background: Adjuvant chemotherapy (ACT) is a well-recognized and well-established treatment for surgically resected non-small cell lung cancer (NSCLC), but its suitability for elderly patients remains controversial. Further investigation is warranted to guide ACT decisions in this demographic. Methods: We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients aged 70 years or older who underwent surgical resection for stage IB, II, or III NSCLC as per the 7th edition of the American Joint Committee on Cancer staging system (AJCC 7th edition). Propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression were employed for statistical analyses. Results: There were 503 participants received ACT in this study of 2,000 patients aged 70 or older with stage IB-IIIB NSCLC who underwent surgical resection without preoperative chemotherapy. Overall, ACT did not significantly correlate with extended overall survival (OS) (P=0.07) compared to non-ACT. After 2:1 PSM, the matched cohort comprised 317 non-ACT and 206 ACT recipients. Post-PSM, the ACT group exhibited improved OS (P=0.044) compared to the non-ACT group. Cox regression analysis identified gender, primary tumor site, histologic grade, N stage, and ACT as independent predictors of OS (P<0.05). Subgroup analysis indicated amplified ACT benefits in individuals aged 70-79 years, male, with N1 stage, or those without radiotherapy. Conclusions: ACT may confer benefits to elderly stage IB-IIIB NSCLC patients, particularly those aged 70-79 years, male, and with N1 stage.

Fully-Fused Indacenodithiophene-Centered Small Molecule n-Type Semiconductors for High-Performance Organic Electronics.

Developing novel n-type organic semiconductors is an enduring research endeavour, given their pivotal roles in organic electronics and their relative scarcity compared to p-type counterparts. In this study, a new strategy was employed to synthesize n-type organic semiconductors featuring fully-fused conjugated backbone. By attaching two sets of adjacent amino and formyl groups to the indacenodithiophene-based central cores and triggering a tandem reaction of Knoevenagel condensation-intramolecular cyclization, DFA1 and DFA2 were realized. The solution-processed organic field effect transistors based on DFA1 exhibited unipolar n-type transport character with a decent electron mobility of ca. 0.10 cm2 V-1 s-1 (ca. 0.038 cm2 V-1 s-1 for DFA2 based devices). When employing DFA1 as a third component in organic solar cells, a high power conversion efficiency of 19.2% can be achieved in ternary devices fabricated with PM6:L8-BO:DFA1. This work paves a new pathway in the molecular engineering of n-type organic semiconductors, propelling relevant research forward.

Recent advancement of sonogenetics: A promising noninvasive cellular manipulation by ultrasound.

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation with ultrasound, these proteins trigger a cascade of cellular activities and functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision and safety in disease treatment. This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, and beyond. Although current literature predominantly emphasizes ultrasonic neuromodulation, this review offers a comprehensive exploration of sonogenetics. We discuss ultrasound properties, the specific ultrasound-sensitive proteins employed in sonogenetics, and the technique's potential in managing conditions such as neurological disorders, cancer, and ophthalmic diseases, and in stem cell therapies. Our objective is to stimulate fresh perspectives for further research in this promising field.

Hydrometeorological conditions drive long-term changes in the spatial distribution of Potamogeton crispus in a subtropical lake.

Globally, anthropogenic disturbance and climate change caused a rapid decline of submerged macrophytes in lake ecosystems. Potamogeton crispus (P. crispus), a species that germinates in winter, explosively expanded throughout many Chinese lakes, yet the underlying mechanism remained unclear. Here, this study examined the long-term changes in the distribution patterns of P. crispus in Lake Gaoyou by combining remote sensing images and hydrometeorological data from 1984 to 2022 and water quality data from 2009 to 2022. It aims to unravel the relationships between the distribution patterns of P. crispus and hydrometeorological and water quality factors. The results showed that the area of P. crispus in Lake Gaoyou showed a slight increase from 1984 to 2009, a marked increase from 2010 to 2019, followed by a decline after 2020. Spatially, P. crispus was primarily distributed in the western and northern parts of Lake Gaoyou, with less distribution in the central and southeastern parts of the lake. Wind speed (WS), temperature (Temp), water level (WL), ammonia nitrogen (NH3-N), and Secchi depth (SD) were identified as the key factors regulating the variation in the P. crispus area in Lake Gaoyou. We found that the P. crispus area showed an increasing trend with increasing Temp, WL, and SD and decreasing WS and NH3-N. The influence of environmental factors on the area of P. crispus in Lake Gaoyou varied among seasons. The results indicated that hydrometeorology (WS, Temp, and WL) may override water quality (NH3-N and SD) in driving the succession of P. crispus distribution. The findings of this study offer valuable insights into the recent widespread expansion of P. crispus in shallow lakes across Eastern China.

Growth Properties and Metabolomic Analysis Provide Insight into Drought Tolerance in Barley (Hordeum vulgare L.).

Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots' metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds.