The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

Bis-piperidine alkaloids from the peels of Areca catechu.

Four new alkaloids, arecatines A-D (1-4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2-4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.

Two new chemical constituents from the aerial parts of Tripterygium wilfordii.

Tripterygium wilfordii has been historically employed as a conventional botanical insecticide and a plant of medicinal significance. A new dihydroagarofuran sesquiterpene (1) and a new acyclic compound (2), along with seven known compounds (3-9), have been isolated from the aerial parts of Tripterygium wilfordii. The identification of the structures of novel compounds were accomplished through comprehensive spectroscopic analyses, encompassing HRESIMS, NMR, UV, IR, and a comparative analysis with spectroscopic data from compounds previously characterised. In in-vitro bioassay, compound 8 exhibited significant inhibitory activity for NO release in LPS-induced RAW 264.7 cells, with an IC50 value of 15.7 µM.

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

The Effect of Dexmedetomidine as a Local Anesthetic Adjuvant for Iliac Fascia Compartment Block on Postoperative Delirium in Elderly Patients Undergoing Elective Hip Surgery.

INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.

The burden of cardiovascular disease attributable to high body mass index-an observational study.

AIM: This study aims to provide a timely and comprehensive estimate of the current burden and temporal trend of cardiovascular disease (CVD) attributable to high body mass index (HBMI). METHODS: We systematically assessed the current burden and temporal trend of CVD attributable to HBMI by calendar year, age, sex, region, nation, socioeconomic status, and specific CVD based on the most recent Global Burden of Disease Study (GBD) 2019. RESULTS: Globally, the numbers of CVD-related disability-adjusted life years (DALYs) and deaths attributable to HBMI has more than doubled from 1990 to 2019. Conversely, the age-standardized rates (ASRs) of CVD-related DALYs and deaths attributable to HBMI showed a slight downward trend, with estimated annual percentage change (EAPC) of -0.18 and -0.43, respectively. The ASRs of CVD-related DALYs and deaths attributable to HBMI were lower in low and high Socio-demographic Index (SDI) regions in 2019, but higher in middle and high-middle SDI regions. The ASRs of CVD-related DALYs and deaths attributable to HBMI showed a downward trend in the high SDI regions from 1990 to 2019, but showed an upward trend in the low and low-middle SDI regions. The leading causes of CVD burden attributable to HBMI were ischemic heart disease, stroke, hypertensive heart disease, and atrial fibrillation/flutter in 2019. CONCLUSION: The CVD burden attributable to HBMI remains a challenging global health concern. Policymakers in high and increasing burden regions can learn from some valuable experiences of low and decreasing burden regions and develop more targeted and specific strategies to prevent and reduce CVD burden attributable to HBMI.

Discovery of Unusual Ajmaline-Macroline Type Bisindole Alkaloids from Alstonia macrophylla by Building Blocks-Based Molecular Networking.

Three unusual ajmaline-macroline type bisindole alkaloids, alsmaphylines A-C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks-based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline-macroline type bisindole alkaloid with an S-shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline-macroline type bisindole alkaloids with N-1-C-21' linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A-C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.

Characteristic chromanone acids from Calophyllum membranaceum: Determination of C-3 configuration and anti-inflammatory activity.

One undescribed homologous furanochromanone (1) featuring a 6/6/5/3 tetracyclic skeleton and four highly oxidized pyranochromanones (2-5), along with a set of four pyranochromanone stereoisomers [(±)-6a and (±)-6b], were isolated from the leaves of Calophyllum membranaceum Gardn. Et Champ. Their structures were elucidated by using spectroscopic data, Snatzke's method, quantum-chemical calculations, and X-ray crystallographic analysis. The correlation of characteristic Cotton effects and specific chemical shifts with C-3 configuration provided a convenient approach to assign the C-3 configuration of 2,3-dimethylchromanones. The stereochemical assignments of 3-OH substituted pyranochromanones by quantum-based NMR methods following single/double MTPA derivatization were consistent with the ECD/NMR prediction, which verified the feasibility and reliability of the proposed empirical rule. The underlying mechanism was further clarified by conformational and molecular orbital analyses. Moreover, biological evaluation and binding assays demonstrated that compound 3 (KD = 0.45 µM) tightly binds to the TLR4-MD2 target, thereby inhibiting the TLR4/MyD88-dependent and -independent signal pathways. This study provides the first evidence that Calophyllum chromanones are a novel structural type of TLR4 inhibitors, exerting their anti-inflammatory effects by disrupting the binding between TLR4 and MD2.

Limonoids from the roots of Melia azedarach and their anti-inflammatory activity.

Twelve undescribed limonoids, meliazedarines J-U (1-12), along with a known one, were isolated from the roots of Melia azedarach. Their structures were elucidated by extensive spectroscopic investigations, X-ray diffraction analyses, and ECD calculations. Compounds 1-8 were identified as ring intact limonoids, while compounds 9-12 were established as ring C-seco ones. The anti-inflammatory potential of compounds 1-4, 6, 8, 9, and 11-13 was evaluated on macrophages. Compounds 1, 3, 4, 6, and 9 significantly suppressed nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, among them compound 3 showed the best inhibitory effect with an IC50 value of 7.07 ± 0.48 µΜ. Furthermore, compound 3 effectively reduced interleukin-1ß secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. The results strongly suggested that limonoids from the roots of M. azedarach might be candidates for treating inflammation-related diseases.

Wrist-ankle acupuncture combined with pain nursing for the treatment of urinary calculi with acute pain.

BACKGROUND: Urological calculi often cause renal colic, which is characterized by paroxysmal or persistent severe pain in the upper abdomen or lumbar region. Development of methods to quickly relieve these pain symptoms has garnered clinical attention. Wrist-ankle acupuncture is a type of floating acupuncture therapy administered at selected points in the carpal and ankle areas, and it has good pain-relieving effects. We used wrist-ankle acupuncture combined with pain nursing for pain intervention in patients with renal calculi to confirm its application and safety. AIM: To study the effect of wrist-ankle acupuncture combined with pain nursing in the treatment of urinary calculi with acute pain. METHODS: Eighty-two patients with urinary calculi with acute pain as the first symptom followed at our hospital from November 2019 to June 2021 were enrolled in the study and classified into two groups according to the odd and even numbers of the visit sequences, each with 41 cases. The control group received a routine nursing intervention and intramuscular injection of nonsteroidal anti-inflammatory drugs, whereas the observation group received pain management nursing and wrist-ankle acupuncture. Subsequently, the pain-relieving effect was compared between the two groups. RESULTS: The score on the visual analog scale (VAS) at 24, 48, and 72 h postintervention was decreased in both groups compared with the baseline data; moreover, the observation group scored significantly lower than the control group on the VAS at each time point after the intervention (P < 0.05). The clinical efficacy at 24 h postintervention was not significantly different between the two groups (P > 0.05). In turn, the pain recurrence rate at 72 h postintervention was lower in the observation group compared with the control group (P < 0.05). Finally, the nursing satisfaction rate in the observation group was significantly higher than that observed in the control group (P < 0.05). No serious adverse reactions occurred during the treatment and the safety of treatment was high in both groups. CONCLUSION: Wrist-ankle acupuncture combined with pain nursing for treating urolithiasis with acute pain effectively alleviated the degree of pain and reduced the recurrence rate, which was worthy of clinical application.

Effect of individualized PEEP titration by ultrasonography on perioperative pulmonary protection and postoperative cognitive function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. METHODS: A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. RESULTS: The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P < 0.05) and value of IL-6 was significantly decreased (P < 0.05) at the corresponding time points. Compared with group C, the MoCA score on day 7 after surgery in Group T was significantly higher (P < 0.05). CONCLUSION: Compared with the traditional ventilation strategy, the individualized ΔP combined with LUS-based PEEP titration in patients with COPD during the perioperative period of laparoscopic surgery can play a better role in lung protection and can improve postoperative cognitive function.

[A new dihydrochalcone from Humulus scandens].

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Monoterpenoid indole alkaloid adducts and dimers from Melodinus fusiformis.

Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative biogenetic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of couplings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection effects on MPP +-injured primary cortical neurons.

The Protective Effect of (-)-Tetrahydroalstonine against OGD/R-Induced Neuronal Injury via Autophagy Regulation.

Here, (-)-Tetrahydroalstonine (THA) was isolated from Alstonia scholaris and investigated for its neuroprotective effect towards oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal damage. In this study, primary cortical neurons were pre-treated with THA and then subjected to OGD/R induction. The cell viability was tested by the MTT assay, and the states of the autophagy-lysosomal pathway and Akt/mTOR pathway were monitored by Western blot analysis. The findings suggested that THA administration increased the cell viability of OGD/R-induced cortical neurons. Autophagic activity and lysosomal dysfunction were found at the early stage of OGD/R, which were significantly ameliorated by THA treatment. Meanwhile, the protective effect of THA was significantly reversed by the lysosome inhibitor. Additionally, THA significantly activated the Akt/mTOR pathway, which was suppressed after OGD/R induction. In summary, THA exhibited promising protective effects against OGD/R-induced neuronal injury by autophagy regulation through the Akt/mTOR pathway.

Global, regional and national burden of alcohol cardiomyopathy from Global Burden of Disease Study 2019.

This study aimed to provide up-to-date and comprehensive estimates on the global alcohol cardiomyopathy (ACM) from 1990 to 2019. Detailed data on the prevalence, disability-adjusted life-years (DALYs), deaths,percentage change in the number of cases and estimated annual percentage change (EAPC) of ACM worldwide from 1990 to 2019 were obtained or calculated from the Global Burden of Disease Study (GBD) 2019. Globally, the estimated prevalent cases of ACM in 2019 were 707,652 [95% uncertainty interval (UI): 545,182-924,392], with a 35.4% (28.2-44.2) increase from 522,616 (95% UI: 394,118-683,206) in 1990, while the age-standardized prevalence rate (ASPR) was slightly decreased with an overall EAPC of - 1.30 (- 1.38 - - 1.22). Similar to ASPR, the global age-standardized DALYs rate and age-standardized death rate (ASDR) also declined, with an EAPC of - 1.12(- 2.09 - - 0.14) and - 1.53(- 2.36 - - 0.70) from 1990 to 2019, respectively. Conversely, the number of ACM-related DALYs cases in 2019 was 2,441,108 (95% UI: 2,046,734-2,782,542), with an increase of 38.8%(2.8-59.9) over the past 30 years, and the number of ACM-related deaths in 2019 was 71,723 (95% UI: 60,167-81,995), with an increase of 33.1% (0.5- 51.9) compared with 1990. A significant variation in the burden of ACM was observed between different regions and countries. Although the ASPR, age-standardized DALYs rate and ASDR slightly decreased from 1990 to 2019, the absolute number of prevalent cases, DALYs cases and deaths significantly increased. This showed that the burden of ACM remains an important global public health concern. Public health policy and decision-makers should develop and implement more effective strategies specific to geographical location to combat and reduce the burden of ACM in the future.

Prinsepia utilis Royle leaf extract: Ameliorative effects on allergic inflammation and skin lesions in allergic contact dermatitis and polyphenolic profiling through UPLC-MS/MS coupled to chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic contact dermatitis (ACD) is a common allergic inflammatory disease that is concomitant with skin swelling, redness, dry itching, and relapses. Prinsepia utilis Royle, a Chinese and Indian folk medicine, is rich in polyphenols with potential anti-inflammatory and skin-protective activities. However, the underlying mechanism of P. utilis leaf (PUL) in the treatment of ACD and its functional basis remains unclear. AIM OF THE STUDY: This study is aimed to explore and reveal the active substances and mechanism of PUL against ACD. MATERIALS AND METHODS: Hyaluronidase inhibitory assay and fluorescein isothiocyanate (FITC)-induced ACD mouse model were performed to assess the antiallergic effects of PUL in vitro and in vivo. Different solvents were applied to obtain multiple PUL extracts. The extracts were further tested for total phenolic content (TPC) and total flavonoid content (TFC) by using spectrophotometric assays. Polyphenolic profiles were analyzed by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), and a simultaneous quantification method was established using UPLC-QTrap-MS/MS through multiple reaction monitoring (MRM) and applied to analyze the pharmacokinetics of the multiple major polyphenols of PUL in mice. RESULTS: The water extract of PUL with the highest TPC/TFC exhibited the strongest antihyaluronidase effect (IC50 = 231.93 µg/mL). In vivo assays indicated that the oral administration of PUL water extract dose-dependently attenuated ACD-like symptoms by decreased interleukin (IL)-4, IL-5, IL-13, IL-33, thymic stromal lymphopoietin, and IgE production, suppressed eosinophil and basophil secretion, and increasing the expression of tight junction (TJ) proteins (claudin-1 [CLDN-1] and occludin). Concomitantly, UPLC-QTOF-MS/MS analysis enabled the identification of 60 polyphenols and the pharmacokinetic parameters of seven quantified constituents of PUL were characterized. Four compounds, trans-p-coumaric acid 4-O-ß-D-glucopyranoside (11), vicenin-2 (21), isoschaftoside (31), and kaempferol 3-O-(2″,6″-di-O-α-L-rhamnopyransoyl)-ß-D-glucopyranoside (38) which displayed satisfactory pharmacokinetic features, were considered as potential effective substances in PUL. CONCLUSIONS: PUL water extract ameliorated the allergic inflammation of ACD by repairing the epithelial barrier and alleviating Th2-type allergic inflammation. The anti-allergic effect of PUL is closely related to its phenolic substances, and compounds 11, 21, 31, and 38 were the active substances of PUL. It revealed that P. utilis could be developed as a new source of antiallergic agents for ACD therapy.

Bixasteroid, a new compound from the fruits of Bixa orellana and its anti-inflammatory activity.

Bixasteroid (1), one new steroid together with five known compounds (2-6), were isolated from the ethyl acetate fraction of ethanol extract of Bixa orellana fruits. All of these known compounds were isolated from the plant for the first time. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of compound 1 was determined by X-ray crystallographic data analysis as well as by the quantum chemical ECD calculations. All the isolated compounds were tested for their anti-inflammatory activities. Compounds 1 and 2 showed inhibiting NO release activities in LPS-induced RAW 264.7 macrophages with the IC50 values of 4.72 ± 0.28 and 5.48 ± 1.48 µM, respectively.

Genome architecture and diverged selection shaping pattern of genomic differentiation in wild barley.

Divergent selection of populations in contrasting environments leads to functional genomic divergence. However, the genomic architecture underlying heterogeneous genomic differentiation remains poorly understood. Here, we de novo assembled two high-quality wild barley (Hordeum spontaneum K. Koch) genomes and examined genomic differentiation and gene expression patterns under abiotic stress in two populations. These two populations had a shared ancestry and originated in close geographic proximity but experienced different selective pressures due to their contrasting micro-environments. We identified structural variants that may have played significant roles in affecting genes potentially associated with well-differentiated phenotypes such as flowering time and drought response between two wild barley genomes. Among them, a 29-bp insertion into the promoter region formed a cis-regulatory element in the HvWRKY45 gene, which may contribute to enhanced tolerance to drought. A single SNP mutation in the promoter region may influence HvCO5 expression and be putatively linked to local flowering time adaptation. We also revealed significant genomic differentiation between the two populations with ongoing gene flow. Our results indicate that SNPs and small SVs link to genetic differentiation at the gene level through local adaptation and are maintained through divergent selection. In contrast, large chromosome inversions may have shaped the heterogeneous pattern of genomic differentiation along the chromosomes by suppressing chromosome recombination and gene flow. Our research offers novel insights into the genomic basis underlying local adaptation and provides valuable resources for the genetic improvement of cultivated barley.