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Sea buckthorn (Hippophae neurocarpa), a plant with both medicinal and edible properties, exhibits high content of serotonin with a unique brown color. Here, we assemble the 1002.54 Mb genome sequence of H. neurocarpa and find that it has evolved from two sequential polyploidizations with four sub-genomes. Based on in vitro enzyme activity and transient overexpression experiments, we confirm that the expression of both HnT5H1 and HnT5H2 genes from tandem duplication contributes to high accumulation of serotonin in sea buckthorn. Furthermore, we verify that the HnGLK1 gene plays a crucial role in continuous chlorophyll accumulation, driving the brown color formation of H. neurocarpa fruit. Collectively, the high-quality genome of H. neurocarpa offers valuable insights into the mechanisms underlying serotonin biosynthesis and abnormal coloration and serves as a valuable resource for further functional genomic studies and molecular breeding efforts in sea buckthorn., (© 2025 Society for Experimental Biology and John Wiley & Sons Ltd.)

Bioplastics, particularly polyhydroxyalkanoates (PHAs), are emerging as promising alternatives to traditional materials due to their biodegradability. This study focuses on the production of PHAs as bioplastics using effluent from hydrogen production in a two-stage Biohythane Pilot Plant, which provides a low-cost substrate. The aim is to optimize production conditions, with Cupriavidus necator TISTR 1335 being used as the PHA producer. Utilizing Response Surface Methodology-Central Composite Design, we explored optimal conditions, revealing peak PHA production at a substrate concentration of 33.51 g COD/L and a pH of 6.87. The predicted optimal PHA concentration was at 3.05 g/L within the established model, closely matching the experimentally validated value of 3.02 g/L, with the overall usage rate of reducing sugars approximately 50-60%. This study underscores the importance of optimizing PHA production conditions and paving the way toward large-scale PHA production., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval and consent to participate: Not applicable. Consent for publication: All the authors agree to the publication of this manuscript., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Surgery can induce severe neuroinflammation and negative emotional symptoms, such as anxiety-like behaviour. We studied whether reactive astrocytes in the zona incerta (ZI) mediate surgery-induced anxiety in mice., Methods: Laparotomy under isoflurane 1.5 vol% was used as a model in adult mice. The role of the ZI in surgery-induced anxiety was evaluated by behavioural tests, optical fibre recordings of neuronal activity, in vivo electrophysiological recordings, chemogenetics, and optogenetics., Results: Operative mice showed increased anxiety-like behaviour. Immunostaining and optical calcium recording revealed that astrocytes were abnormally activated in the ZI. Pharmacologic (F 3, 15 =5.837, P=0.044) or genetic manipulation (open field test: t 7.41 =3.66, P=0.007; elevated plus maze [EPM]: t 10 =2.70, P=0.022) of astrocyte activation in the ZI relieved anxiety-like behaviour in surgery-treated mice. Compared with the sham group, the surgery group showed increased extrasynaptic GABA concentrations and decreased GABA transporter-3 (GAT-3) expression, and inactivation of GABAergic neurones in the ZI. Upregulating GAT-3 in ZI astrocytes (OFT: t 10.83 =2.91, P=0.014; EPM: t 9.15 =3.55, P=0.006) or activating the GABAergic projection from ZI to the median raphe nucleus (ZI GABA →median raphe nucleus) (EPM: entries: F 1, 24 =3.45, P=0.027; time: F 1, 25 =4.07, P=0.043) ameliorated surgery-induced anxiety., Conclusions: Reactive astrocytes in the zona incerta mediate surgery-induced anxiety, possibly by regulating GAT-3-mediated GABA homeostasis and inactivating ZI GABA →median raphe nucleus projections in mice., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Burns are common traumatic injuries affecting many people worldwide. Development of specialized burn units, advances in acute care modalities, and burn prevention programs have successfully reduced the mortality rate of severe burns. Autologous skin grafting has been considered as the gold standard for wound coverage after the removal of burned skin. For full-thickness burns of a larger scale, however, the autograft donor site may be quickly exhausted, so that alternative skin coverage is necessary. Although rapid progress has been made in the development of skin substitutes for burn wounds during the last decade, no skin substitute has fulfilled the criteria as a perfect replacement for the damaged skin. Extracellular matrix (ECM) derived components have emerged as a source for the engineering of biomaterials capable of inducing desirable cell-specific responses and one of the most promising biomaterials for burn wound healing. Among these, acellular dermal matrix, small intestinal submucosa, and amniotic membrane have been applied to treat burn wounds with acceptable outcomes. This review has explored the use of biomaterials derived from naturally occurring ECM and their derivatives for approaches aiming to promote burn wound healing, and summarized the ECM-based wound dressings products applicable in burn wound and postburn scar contracture to date., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Jilin Province is an important ecological security barrier in Northeast China as it is located at the junction of the Northeast forest belts and the northern sand prevention belts. In recent years, Jilin Province has actively carried out ecological protection and restoration projects, resulting in a continuous improvement trend for the overall ecological environment. However, the evolution patterns and mechanisms of habitat quality are largely unkown. We applied the InVEST model and geographic detector method to analyze the changes in habitat quality and evaluate the main driving factors from 2000 to 2020. The results showed that the average habitat quality in Jilin Province showed a slight downward trend, and that the spatial heterogeneity characteristics of habitat quality in east and west gradually increased. The degree of habitat degradation presented a single nuclear radiation pattern centered on Changchun City. Vegetation factors and terrain factors were the first and secondary causes of spatial heterogeneity of habitat quality, respectively. The average habitat quality within the eco-redline of Jilin Province was showing an increasing trend year by year, which was consistent with the overall distribution of regions with extremely high habitat quality levels. There was a local spatial dislocation (the phenomenon of extremely high habitat quality levels not within the eco-redline) in the eastern part of Jilin Province. Our results could provide reference basis for ecosystem protection and the spatial pattern optimization.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The pathogenesis of vascular dementia (VD) is complex, and currently, no effective treatments have been recommended. Floralozone is a colorless liquid first discovered in Lagotis Gaertn. Recently, its medicinal value has been increasingly recognized. Our previous study has demonstrated that Floralozone can improve cognitive dysfunction in rats with VD by regulating the transient receptor potential melastatin 2 (TRPM2) and N-methyl-D-aspartate receptor (NMDAR) signaling pathways. However, the mechanism by which Floralozone regulates TRPM2 and NMDAR to improve VD remains unclear. AMP-activated protein kinase (AMPK) is an energy regulator in vivo; however, its role of AMPK activation in stroke remains controversial. MiR-7a-5p has been identified to be closely related to neuronal function., Purpose: To explore whether Floralozone can regulate the miR-7a-5p level in vivo through AMPKα2 activation, affect the TRPM2 and NR2B expression levels, and improve VD symptoms., Methods: The VD model was established by a modified bilateral occlusion of the common carotid arteries (2-VO) of Sprague-Dawley (SD) rats and AMPKα2 KO transgenic (AMPKα2 -/- ) mice. Primary hippocampal neurons were modeled using oxygen and glucose deprivation (OGD). Morris water maze (MWM) test, hematoxylin-eosin staining (HE staining), and TUNEL staining were used to investigate the effects of Floralozone on behavior and hippocampal morphology in rats. Minichromosome maintenance complex component 2(MCM2) positive cells were used to investigate the effect of Floralozone on neurogenesis. Immunofluorescence staining, qRT-PCR, and western blot analysis were used to investigate the effect of Floralozone on the expression levels of AMPKα2, miR-7a-5p, TRPM2, and NR2B., Results: The SD rat experiment revealed that Floralozone improved spatial learning and memory, improved the morphology and structure of hippocampal neurons, reduced apoptosis of hippocampal neurons and promoted neurogenesis in VD rats. Floralozone could increase the miR-7a-5p expression level, activate AMPKα2 and NR2B expressions, and inhibit TRPM2 expression in hippocampal neurons of VD rats. The AMPKα2 KO transgenic (AMPKα2 -/- ) mice experiment demonstrated that Floralozone could regulate miR-7a-5p, TRPM2, and NR2B expression levels through AMPKα2 activation. The cell experiment revealed that the TRPM2 and NR2B expression levels were regulated by miR-7a-5p, whereas the AMPKα2 expression level was not., Conclusion: Floralozone could regulate miR-7a-5p expression level by activating the protein expression of AMPKα2, control the protein expression of TRPM2 and NR2B, improve the morphology and structure of hippocampus neurons, reduce the apoptosis of hippocampus neurons, promote neurogenesis and improve the cognitive dysfunction., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript was approved by all authors for publication., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: MYC transcription factors are the basic regulators of the jasmonic acid signaling pathway and play important roles in plant growth and development and the response to adverse stress. In recent years, severe winter freezing and late spring frost in the main planting area of walnut in Xinjiang have affected the growth and development of walnut, which has become a prominent problem restricting walnut production. Xinjiang wild walnut is the only remaining wild species of walnuts in China, which contains a lot of genes with excellent traits, and is important for the cultivation and breeding. Methods: In this paper, the physicochemical properties and bioinformatics of MYC transcription factor members in walnut were analyzed, and the nine MYC were screened from the transcriptome data under low temperature stress. At last, we study the subcellular localizations and the expression patterns of the nine MYC members in Xinjiang wild walnut. Results: The results revealed that 30 MYC members were identified from published walnut whole-genome data, and their evolutionary relationships with Arabidopsis and poplar were divided into six groups according to clustering analysis, among which JrMYC22 and JrMYC23 had high homology with PtrMYC2b , which is induced by jasmonic acid in response to low-temperature stress. Walnut MYC members are unevenly distributed on 12 chromosomes. The prediction of promoter cis-acting elements of walnut MYC transcription factor family members revealed that cis-acting elements related to jasmonic acid and lowtemperature stress were the ones with the greatest number of members, with 12. In addition, all nine MYC family members in Xinjiang wild walnut plants responding to low-temperature stress exhibited strong fluorescence responses in the nucleus. The expression levels of these members in response to low-temperature stress revealed that JrMYC28, JrMYC31, JrMYC33, JrMYC34, and JrMYC35 were highly expressed, and it was hypothesized that JrMYC28, JrMYC31, JrMYC33, JrMYC34, and JrMYC35 might play a key role in the response to lowtemperature stress. Discussion: The results of this study provide a theoretical basis for further research on the functional mechanisms of the MYC transcription factor family members in walnut., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Ma, Zhao, Han and Liu.)

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

Innate defensive behavior is important for animal survival. The Vglut 2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut 2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut 2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut 2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTA Vglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Zintl-phase materials have attracted significant research interest owing to the interplay of magnetism and strong spin-orbit coupling, providing a prominent material platform for axion electrodynamics. Here, we report the single-crystal growth, structure, magnetic and electrical/thermal transport properties of the antiferromagnet layer Zintl-phase compound β-EuIn 2 As 2 . Importantly, the new layered structure of β-EuIn 2 As 2 , in rhombohedral ( R 3̄ m ) symmetry, contains triangular layers of Eu 2+ ions. The in-plane resistivity ρ ( H , T ) measurements reveal metal behavior with an antiferromagnetic (AFM) transition ( T N ∼ 23.5 K), which is consistent with the heat capacity C p ( H , T ) and magnetic susceptibility χ ( H , T ) measurements. Negative MR was observed in the temperature range from 2 K to 20 K with a maximum MR ratio of 0.06. Unique 4f 7 J = S = 7/2 Eu 2+ spins were supposed magnetically order along the c -axis. The Seebeck coefficient shows a maximum thermopower | S max | of about 40 μV K -1 . The kink around 23 K in the Seebeck coefficient originates from the effect of the antiferromagnetic phase on the electron band structure, while the pronounced thermal conductivity peak at around 10 K is attributed to the phonon-phonon Umklapp scattering. The results suggest that the Eu 2+ spin arrangement plays an important role in the magnetic, electrical, and thermal transport properties in β-EuIn 2 As 2 , which might be helpful for future potential technical applications.

Background: Working memory refers to our ability to temporarily store and process information, and it is crucial for efficient cognition and motor control. In the context of badminton matches, athletes need to make quick decisions and reactions in rapidly changing situations. Athletes with strong working memory capacity can better process this information and translate it into actual motor performance. Although previous research has demonstrated that exercise can improve brain function and structure, it remains unclear how the brain functions of athletes engaged in long-term professional training are specifically involved in performing working memory tasks., Method: In this study, we assessed behavioral performance and cerebral oxygenation in the prefrontal lobe, using functional near-infrared spectroscopy, with 22 athletes and 30 non-athletes. Each participant was evaluated while performing 1-back, 2-back, and 3-back tasks. The area under the curve (AUC) of HbO (oxyhemoglobin) is used as an indicator of cortical brain oxygenation., Results: The behavioral performance results indicated no difference between badminton athletes and non-athletes in the n-back task. We observed significantly different activation in channels of left FPA, right DLPFC, and left VLPFC when performing 3-back tasks. Brain activation indicated that long-term training in badminton caused a better performance in high-load working memory tasks., Conclusions: Long-term professional training in badminton primarily activates the left frontal-parietal attention network (left FPA), right dorsolateral prefrontal cortex (right DLPFC), and left ventrolateral prefrontal cortex (left VLPFC) during working memory tasks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Plastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH 3 -(CH 2 ) n-1 ) 2 NH 2 X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔS r  ~ 400 J kg -1  K -1 at 0.08 GPa and adiabatic temperature change ΔT r  ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals., (© 2024. The Author(s).)

The establishment of a stable animal model for intrauterine adhesion (IUA) can significantly enhance research on the pathogenesis and pathological changes of this disease, as well as on the development of innovative therapeutic approaches. In this study, three different modeling methods, including phenol mucilage combined mechanical scraping, ethanol combined mechanical scraping and ethanol modeling alone were designed. The morphological characteristics of the models were evaluated. The underlying mechanisms and fertility capacity of the ethanol modeling group were analyzed and compared to those of the sham surgery group. All three methods resulted in severe intrauterine adhesions, with ethanol being identified as a reliable modeling agent and was subsequently subjected to further evaluation. Immunohistochemistry and RT-PCR results indicated that the ethanol modeling group exhibited an increase in the degree of fibrosis and inflammation, as well as a significant reduction in endometrial thickness, gland number, vascularization, and endometrial receptivity, ultimately resulting in the loss of fertility capacity. The aforementioned findings indicate that the intrauterine perfusion of 95 % ethanol is efficacious in inducing the development of intrauterine adhesions in rats. Given its cost-effectiveness, efficacy, and stability in IUA formation, the use of 95 % ethanol intrauterine perfusion may serve as a novel platform for evaluating innovative anti-adhesion materials and bioengineered therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background and Objective: Since its initial report by James Parkinson in 1817, Parkinson's disease (PD) has remained a central subject of research and clinical advancement. The disease is estimated to affect approximately 1% of adults aged 60 and above. Deep brain stimulation, emerging as an alternative therapy for end-stage cases, has offered a lifeline to numerous patients. This review aimed to analyze publications pertaining to the impact of deep brain stimulation on the motor pathway in patients with PD over the last decade., Methods: Data were obtained from the Web of Science Core Collection through the library of Huazhong University of Science and Technology (China). The search strategy encompassed the following keywords: "deep brain stimulation", "Parkinson's disease", "motor pathway", and "human", from January 1, 2012, to December 1, 2022. Additionally, this review visualized the findings using the Citespace software., Results: The results indicated that the United States, the United Kingdom, Germany, and China were the primary contributors to this research field. University College London, Capital Medical University, and Maastricht University were the top 3 research institutions in the research area. Tom Foltynie ranked first with 6 publications, and the journals of Brain and Brain Stimulation published the greatest number of relevant articles. The prevailing research focal points in this domain, as determined by keywords "burst analysis", "encompassed neuronal activity", "nucleus", "hyper direct pathway", etc. CONCLUSION: This study has provided a new perspective through bibliometric analysis of the deep brain stimulation therapy for treating patients with PD, which can shed light on future research to advance our comprehension of this particular field of study., (© 2023. Huazhong University of Science and Technology.)

The recurrence rate for severe intrauterine adhesions is as high as 60%, and there is still lack of effective prevention and treatment. Inspired by the nature of uterus, we have developed a bilayer scaffold (ECM-SPS) with biomimetic heterogeneous features and extracellular matrix (ECM) microenvironment of the uterus. As proved by subtotal uterine reconstruction experiments, the mechanical and antiadhesion properties of the bilayer scaffold could meet the requirement for uterine repair. With the modification with tissue-specific cell-derived ECM, the ECM-SPS had the ECM microenvironment signatures of both the endometrium and myometrium and exhibited the property of inducing stem cell-directed differentiation. Furthermore, the ECM-SPS has recruited more endogenous stem cells to promote endometrial regeneration at the initial stage of repair, which was accompanied by more smooth muscle regeneration and a higher pregnancy rate. The reconstructed uterus could also sustain normal pregnancy and live birth. The ECM-SPS may thereby provide a potential treatment for women with severe intrauterine adhesions.

Clinically, cardiac dysfunction is a key component of sepsis-induced multi-organ failure. Mitochondria are essential for cardiomyocyte homeostasis, as disruption of mitochondrial dynamics enhances mitophagy and apoptosis. However, therapies targeted to improve mitochondrial function in septic patients have not been explored. Transcriptomic data analysis revealed that the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the heart was the most significantly decreased in the cecal ligation puncture-treated mouse heart model, and PPARα was the most notably decreased among the three PPAR family members. Male Ppara fl/fl (wild-type), cardiomyocyte-specific Ppara-deficient (Ppara ΔCM ), and myeloid-specific Ppara-deficient (Ppara ΔMac ) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce endotoxic cardiac dysfunction. PPARα signaling was decreased in LPS-treated wild-type mouse hearts. To determine the cell type in which PPARα signaling was suppressed, the cell type-specific Ppara-null mice were examined. Cardiomyocyte- but not myeloid-specific Ppara deficiency resulted in exacerbated LPS-induced cardiac dysfunction. Ppara disruption in cardiomyocytes augmented mitochondrial dysfunction, as revealed by damaged mitochondria, lowered ATP contents, decreased mitochondrial complex activities, and increased DRP1/MFN1 protein levels. RNA sequencing results further showed that cardiomyocyte Ppara deficiency potentiated the impairment of fatty acid metabolism in LPS-treated heart tissue. Disruption of mitochondrial dynamics resulted in increased mitophagy and mitochondrial-dependent apoptosis in Ppara △CM mice. Moreover, mitochondrial dysfunction caused an increase of reactive oxygen species, leading to increased IL-6/STAT3/NF-κB signaling. 3-Methyladenine (3-MA, an autophagosome formation inhibitor) alleviated cardiomyocyte Ppara disruption-induced mitochondrial dysfunction and cardiomyopathy. Finally, pre-treatment with the PPARα agonist WY14643 lowered mitochondrial dysfunction-induced cardiomyopathy in hearts from LPS-treated mice. Thus, cardiomyocyte but not myeloid PPARα protects against septic cardiomyopathy by improving fatty acid metabolism and mitochondrial dysfunction, thus highlighting that cardiomyocyte PPARα may be a therapeutic target for the treatment of cardiac disease., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca 2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca 2+ ([Ca 2+ ] i ) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca 2+ ] i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca 2+ ] i against MI injury in neonatal rat cardiomyocytes and a rat model., Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca 2+ ] i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured., Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca 2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG., Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca 2+ ] i ., Competing Interests: The authors declare that there are no conflicts of interest.A conflicting interest exists when professional judgement concerning a primary interest (such as patient's welfare or the validity of research) may be influenced by a secondary interest (such as financial gain or personal rivalry). It may arise for the authors when they have financial interest that may influence their interpretation of their results or those of others. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (© 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

To explore the effect of monoculture and mixture sowing artificial grassland on the photosynthetic characteristics of Leymus chinensis and Medicago sativa , we determined the diurnal variation of photosynthetic properties of L. chinensis and M. sativa under different treatments. The results showed that the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type' in monoculture, the stomatal conductance of M. sativa showed 'unimodal type', and the stomatal conductance and water use efficiency of L. chinensis showed 'bimodal type'. Under the mixed sowing treatment, the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type', the stomatal conductance and water use efficiency of L. chinensis showed 'unimodal type', and the stomatal conductance of M. sativa showed 'bimodal type'. The peak photosynthetic rate of L. chinensis under mixture was signi-ficantly higher than that under monoculture, being 17.72 and 13.65 μmol CO 2 ·m -2 ·s -1 , respectively. Under monoculture and mixture sowing treatments, the chlorophyll content of L. chinensis was higher than that of M. sativa , nitrogen content of the leaves of L. chinensis was lower than that of M. sativa , and the nitrogen content in the leaves of mixture sowing L. chinensis was significantly higher than that of monoculture sowing L. chinensis , which were 27.60 and 22.55 g·kg -1 , respectively. Net photosynthetic rates of L. chinensis and M. sativa were significantly positively correlated with stomatal conductance and transpiration rate, and significantly negatively correlated with intercellular CO 2 concentration under different planting methods. Net photosynthetic rate of M. sativa was significantly positively correlated with blade temperature and water use efficiency. In summary, mixed sowing was beneficial to enhance nitrogen content of L. chinensis . Our results provided a theoretical basis for the response of the photosynthetic characteristics of forage to planting mode of artificial grassland.

This study aimed to determine whether the abnormal deep layer of dartos fascia plays an important role in buried penis. Forty-nine patients with buried penis were treated with anatomical resection of the deep layer of dartos fascia under a microscope. Penile length was measured before and after completely resecting the deep layer to investigate the role of this layer in penile retraction. The superficial and deep layers of dartos fascia were collected from 49 patients with buried penis, the normal superficial layers were collected from 25 children/adults who underwent circumcision for nonmedical reasons, and the normal deep layers were collected from 20 adult cadavers. The penile fascia samples were stained with hematoxylin-eosin, Masson's trichrome, Sirius red, and Verhoeff's Van Gieson, and subjected to immunohistochemical examination and scanning electron microscopy. The penile shaft (mean ± standard deviation) was found to be significantly elongated after resecting the deep layer compared with that before resection (6.8 ± 1.9 cm vs 6.0 ± 1.6 cm, P < 0.001). An abnormal deep layer of dartos fascia characterized by disordered and fragmented elastic fibers was observed in 87.8% (43/49) of buried penis samples, whereas no abnormal deep layer was observed in normal penises from cadavers (0/20, P < 0.001). Thus, the abnormal deep layer of dartos fascia plays an important role in the buried penis. Its resection is helpful for avoiding recurrence., (Copyright © 2023 Copyright: © The Author(s)(2023).)

The leading mechanism for the formation of O 2 in photosystem II (PSII) has, during the past decade, been established as the so-called oxyl-oxo mechanism. In that mechanism, O 2 is formed from a binding between an oxygen radical (oxyl) and a bridging oxo group. For the case of higher plants, that mechanism has recently been criticized. Instead, a nucleophilic attack of an oxo group on a five-coordinated Mn(V)═O group forming O 2 has been suggested in a so-called water-unbound (WU) mechanism. In the present study, the WU mechanism has been investigated. It is found that the WU mechanism is just a variant of a previously suggested mechanism but with a reactant and a transition state that have much higher energies. The addition of a water molecule on the empty site of the Mn(V)═O center is very exergonic and leads back to the previously suggested oxyl-oxo mechanism.

The neural circuit mechanisms underlying postoperative cognitive dysfunction (POCD) remain elusive. We hypothesized that projections from the medial prefrontal cortex (mPFC) to the amygdala are involved in POCD. A mouse model of POCD in which isoflurane (1.5%) combined with laparotomy was used. Virally assisted tracing techniques were used to label the relevant pathways. Fear conditioning, immunofluorescence, whole-cell patch-clamp recordings, and chemogenetic and optogenetic techniques were applied to investigate the role of mPFC-amygdala projections in POCD. We find that surgery impairs memory consolidation but not retrieval of consolidated memories. In POCD mice, the glutamatergic pathway from the prelimbic cortex to the basolateral amygdala (PL-BLA) shows reduced activity, whereas the glutamatergic pathway from the infralimbic cortex to the basomedial amygdala (IL-BMA) shows enhanced activity. Our study indicates that the hypoactivity in the PL-BLA pathway interrupts memory consolidation, whereas the hyperactivity in the IL-BMA promotes memory extinction, in POCD mice., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Diabetic cardiomyopathy (DCM) is a kind of idiopathic heart disease, which is one of the main complications of diabetes and seriously threatens the life of diabetic patients. Rubiadin, an anthraquinone compound extracted from the stems and roots of rubiaceae, has been widely discussed for its anti-diabetes, anti-oxidation and other pharmacological effects. However, Rubiadin can cause drug-induced liver injury. Therefore, A-cycloglycosylated derivative of Rubiadin (ACDR) was obtained by modifying its structure. The purpose of this study was to investigate the effect of ACDR on DCM cardiac injury and its mechanism. The DCM animal model was established by streptozotocin, and the success of DCM was verified by blood glucose level, echocardiographic evidence of impaired myocardial functions along with enhanced myocardial fibrosis. We performed liver function tests, morphological staining of the heart and tests for oxidative stress to evaluate cardiac functional and structural changes. Finally, the expression of Na + /H + exchanger (NHE1) protein was analyzed by immunohistochemistry and western bolt, and the expression of hairy/enhancer-of-split related with YRPW motif 1 (Hey1) and P-p38 protein was detected by immunofluorescence chemistry and western blotting. The results showed that ACDR can improve cardiac dysfunction, reduce myocardial injury, reduce oxidative stress, and protect the liver in DCM rats. Interestingly, all variations were countered by LiCl. Our study suggests that, along with controlling hyperglycemia, ACDR may improve DCM by reducing NHE1 expression, further inhibiting P-p38 activity and increasing Hey1 expression to reduce oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo / in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD., Competing Interests: This manuscript has been approved by all coauthors. It has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (© 2023 The Authors.)

Two new highly functionalized cembrane diterpenoids named ximaolobophytolides A (1) and B (2) as minor components, together with seven related known compounds (3-9), have been isolated and identified from the Ximao soft coral Lobophytum sp. They were characterized by the presence of an α-methylene-γ-lactone moiety. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the absolute configurations of these two new compounds were elucidated by the combination of quantum mechanical (QM)-NMR and time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculation approaches. In the anti-tumor bioassays, compounds 3-9 showed moderate to significant inhibitory effects (IC 50 values ranging from 29.66 to 0.39 μM) against the proliferations of five tumor cells HEL, A549, H1975, MDA-MB-231, and H1299. It might be worthy to point out that compounds 4, 7, and 8 exhibited better anti-tumor activities than that of the positive control Doxorubicin., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Blue fluorescent carbon dots (PCDs) were prepared by hydrothermal method with Partridge tea. The ethanol extract of Partridge tea (PEE) was found to emit red fluorescence. Thus, a novel ratiometric sensor was constructed by simply mixing the two fluorophores derived from Partridge tea. The presence of tetracycline (TET) at lower concentrations enhanced the emission peak at 508 nm of PCDs and had a negligible effect on the emission peak at 680 nm of PEE. TET at higher concentrations led to  quenching  both the fluorescence of PCDs and PEE via inner filter effect and fluorescence resonance energy transfer, separately. Good linearities for the detection of TET were obtained in the ranges 0.67 to 15.00 μM and 33.33 to 266.67 μM, with limit of detection of 0.095 μM. The sensor was successfully applied to detect TET in lake water and milk samples with good recoveries ranging from 93.27 ± 4.04% to 107.30 ± 6.16%. This study provided a simple, selective, sensitive, rapid, and environmentally friendly method of monitoring TET residues in the environment and food., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones., (© 2023. The Author(s).)

The present investigation of the South China Sea soft coral Sarcophyton trocheliophorum resulted in the discovery of six new polyoxygenated diterpenes, namely sartrocheliols A-E ( 1 , 3 , 5 - 8 ) along with four known ones, 2 , 4 , 9 , and 10 . Based on extensive spectroscopic data analysis, sartrocheliol A ( 1 ) was identified as an uncommon capnosane diterpene, while sartrocheliols B-E ( 3 , 5 - 8 ) were established as cembrane diterpenes. They displayed diverse structural features not only at the distinctly different carbon frameworks but also at the various types of heterocycles, including the epoxide, γ-lactone, furan, and pyran rings. Moreover, their absolute configurations were determined by a combination of quantum mechanical-nuclear magnetic resonance (QM-NMR) approach, modified Mosher's method, and X-ray diffraction analysis. In the anti-tumor bioassay, compound 4 exhibited moderate cytotoxic activities against A549, H1975, MDA-MB-231, and H1299 cells with the IC 50 values ranging from 26.3 to 47.9 μM.

Introduction: The widespread use of smartphones has triggered concern over problematic smartphone use (PSPU), as well as the need to elucidate its underlying mechanisms. However, the correlation between cortical activation and deficient inhibitory control in PSPU remains unclear., Methods: This study examined inhibitory control using the color-word matching Stroop task and its cortical-activation responses using functional near-infrared spectroscopy (fNIRS) in college students with PSPU ( n = 56) compared with a control group ( n = 54)., Results: At the behavioral level, Stroop interference, coupled with reaction time, was significantly greater in the PSPU group than in the control group. Changes in oxygenated hemoglobin (Oxy-Hb) signals associated with Stroop interference were significantly increased in the left ventrolateral prefrontal cortex, left frontopolar area, and bilateral dorsolateral prefrontal cortex (DLPFC). Moreover, the PSPU group had lower Oxy-Hb signal changes associated with Stroop interference in the left-DLPFC, relative to controls., Discussion: These results provide first behavioral and neuroscientific evidence using event-related fNIRS method, to our knowledge, that college students with PSPU may have a deficit in inhibitory control associated with lower cortical activation in the left-DLPFC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiang, Lin, Song, Hu and Hou.)

Ultrasound-mediated microbubble cavitation (UMMC) induces therapeutic angiogenesis to treat ischemic diseases. This study aimed to investigate whether diagnostic UMMC alleviates diabetic cardiomyopathy (DCM) and, if so, through which mechanisms. DCM model was established by injecting streptozocin into rats to induce hyperglycemia, followed by a high-fat diet. The combined therapy of cation microbubble with low-intensity diagnostic ultrasound (frequency = 4 MHz), with a pulse frequency of 20 Hz and pulse length (PL) of 8, 18, 26, or 36 cycles, was given to rats twice a week for 8 consecutive weeks. Diagnostic UMMC therapy with PL at 8, 18, and 26 cycles, but not 36 cycles, dramatically prevented myocardial fibrosis, improved heart functions, and increased angiogenesis, accompanied by increased levels of PI3K, Akt, and eNOS proteins in the DCM model of rats. In cultured endothelial cells, low-intensity UMMC treatment (PL = 3 cycles, sound pressure level = 50%, mechanical index = 0.82) increased cell viability and activated PI3K-Akt-eNOS signaling. The combination of diagnostic ultrasound with microbubble destruction dose-dependently promoted angiogenesis, thus improving heart function through PI3K-Akt-eNOS signaling in diabetes. Accordingly, diagnostic UMMC therapy should be considered to protect the heart in patients with diabetes., (© 2022 International Federation for Cell Biology.)

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor critical for systemic lipid homeostasis, has been shown closely related to cardiac remodeling. However, the roles of cardiomyocyte PPARα in pressure overload-induced cardiac remodeling remains unclear because of lacking a cardiomyocyte-specific Ppara-deficient (Ppara ΔCM ) mouse model. This study aimed to determine the specific role of cardiomyocyte PPARα in transverse aortic constriction (TAC)-induced cardiac remodeling using an inducible Ppara ΔCM mouse model. Ppara ΔCM and Ppara fl/fl mice were randomly subjected to sham or TAC for 2 weeks. Cardiomyocyte PPARα deficiency accelerated TAC-induced cardiac hypertrophy and fibrosis. Transcriptome analysis showed that genes related to fatty acid metabolism were dramatically downregulated, but genes critical for glycolysis were markedly upregulated in Ppara ΔCM hearts. Moreover, the hypertrophy-related genes, including genes involved in extracellular matrix (ECM) remodeling, cell adhesion, and cell migration, were upregulated in hypertrophic Ppara ΔCM hearts. Western blot analyses demonstrated an increased HIF1α protein level in hypertrophic Ppara ΔCM hearts. PET/CT analyses showed an enhanced glucose uptake in hypertrophic Ppara ΔCM hearts. Bioenergetic analyses further revealed that both basal and maximal oxygen consumption rates and ATP production were significantly increased in hypertrophic Ppara fl/fl hearts; however, these increases were markedly blunted in Ppara ΔCM hearts. In contrast, hypertrophic Ppara ΔCM hearts exhibited enhanced extracellular acidification rate (ECAR) capacity, as reflected by increased basal ECAR and glycolysis but decreased glycolytic reserve. These results suggest that cardiomyocyte PPARα is crucial for the homeostasis of both energy metabolism and ECM during TAC-induced cardiac remodeling, thus providing new insights into potential therapeutics of cardiac remodeling-related diseases., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Citronellal (CT) is an acyclic monoterpene aldehyde isolated from lemon citronella, which could ameliorate vascular endothelial dysfunction in atherosclerosis in our previous study, however, whether CT can alleviate vascular endothelial dysfunction related with type 2 diabetes (T2DM) is still unknown. So, we investigated the role of CT in vascular dysfunction related to T2DM and the mechanism involved. T2DM rat model was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) (60 mg/kg) to rats fed with high-fat diet (HFD) (4 weeks). After treated with CT (150 mg/kg/d), both the thoracic aorta injury and micro-vascular pathological injury in T2DM rats ex vivo were alleviated, and the oxidative stress in T2DM rats treated with CT were attenuated, manifested as increased content of endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD), and decreased content of malondialdehyde (MDA). Furthermore, CT (15 μg/L) increased the migration capacity of human umbilical vein endothelial cells (HUVECs) under high glucose circumstance (30 mM), and increased the endothelial-dependent relaxation in thoracic aorta isolated from T2DM rats in vitro. Finally, all of these effects of CT were blocked by fingolimod (FTY720), a sphingosine-1-phosphate receptor agonist, and the expression of sphingosine-1-phosphate receptor 1 (S1P1) was increased by CT. In conclusion, CT improved vascular function through S1P/S1P1 signaling pathway., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Pinus tabuliformis adapts to cold climate with dry winter in northern China, serving as important commercial tree species. The TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTOR family(TCP)transcription factors were found to play a role in the circadian clock system in Arabidopsis. However, the role of TCP transcription factors in P. tabuliformis remains little understood., Results: In the present study, 43 TCP genes were identified from P. tabuliformis genome database. Based on the phylogeny tree and sequence similarity, the 43 TCP genes were classified into four groups. The motif results showed that different subfamilies indeed contained different motifs. Clade II genes contain motif 1, clade I genes contain motif 1, 8, 10 and clade III and IV contain more motifs, which is consistent with our grouping results. The structural analysis of PtTCP genes showed that most PtTCPs lacked introns. The distribution of clade I and clade II on the chromosome is relatively scattered, while clade III and clade IV is relatively concentrated. Co-expression network indicated that PtTCP2, PtTCP12, PtTCP36, PtTCP37, PtTCP38, PtTCP41 and PtTCP43 were co-expressed with clock genes in annual cycle and their annual cycle expression profiles both showed obvious seasonal oscillations. PtTCP2, PtTCP12, PtTCP37, PtTCP38, PtTCP40, PtTCP41, PtTCP42 and PtTCP43 were co-expressed with clock genes in diurnal cycle. Only the expression of PtTCP42 showed diurnal oscillation., Conclusions: The TCP gene family, especially clade II, may play an important role in the regulation of the season and circadian rhythm of P. tabuliformis. In addition, the low temperature in winter may affect the diurnal oscillations., (© 2022. The Author(s).)

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag + Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing., Competing Interests: This manuscript has been approved by all coauthors. It has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (© 2022 The Authors.)

The medical usage of Doxorubicin (DOX) as a chemotherapeutic agent is restricted owing to its cardiotoxic properties. This study was designed to explore the effect and underlying mechanisms of Citronellal (CT) on DOX-related cardiotoxicity in rats. Rats were divided into six groups: control, DOX, CT, Lithium chloride (LiCl) (a Na+/H+exchanger-1 [NHE1] activator), DOX + CT, and DOX + CT + LiCl. To induce cardiotoxicity, a cumulative dose of 15 mg/kg DOX was intraperitoneally injected into rats. CT (150 mg/kg) and LiCl (1 mg/kg) were given daily by oral gavage for 6 weeks. CT improved cardiac functional parameters and attenuated the cardiac pathological changes induced by DOX. Further study indicated that CT administration regulated the levels of oxidative stress and apoptosis-related factors and in myocardial tissues, reducing cell per-oxidative damage and apoptosis. Besides this, CT attenuated DOX-induced NHE1 upregulation, and the preventive effects of CT against DOX-induced cardiotoxicity were abrogated by the concurrent administration of LiCl. These results demonstrate that CT could ameliorate DOX-induced cardiotoxicity by inhibiting the NHE1-mediated oxidative stress, apoptosis in rats., (© 2021 Wiley Periodicals LLC.)