Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines.

Chiral amines are commonly used in the pharmaceutical and agrochemical industries1. The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods1,2. Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version3-5. Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning.

Novel MAXPOWER biological antibacterial liquid for eradicating oral Helicobacter pylori.

BACKGROUND: Eradication of oral Helicobacter pylori (H. pylori) not only reduces the infection rate from the transmission route but also improves the success rate of intragastric eradication. MAXPOWER Biological Bacteriostatic Liquid, developed in our previous work, is a composite biological preparation with strong antibacterial ability and unique antibacterial mechanism. The present study evaluated the efficacy of the MAXPOWER biocontrol solution on H. pylori and its success rate in eradicating oral H. pylori in clinical patients. METHODS: Live-dead cell staining and hemolysis test were used to evaluate the cellular safety of MAXPOWER biocontrol solution; plate spreading, live-dead bacterial staining, and scanning electron microscopy methods were used to evaluate its antimicrobial effect against H. pylori. Transcriptomics was used to analyze the changes in H. pylori genes before and after treatment. After seven days of gavage treatment, H&E staining and mice feces were collected for 16SrDNA sequencing to evaluate the animals' safety. Oral H. pylori-positive patients were randomized to be given a placebo and MAXPOWER Bio-Bacteriostatic Liquid gargle for seven days to evaluate the effect on oral H. pylori eradication. RESULTS: In vitro tests demonstrated that this product has excellent biocompatibility and hemocompatibility and can effectively eradicate oral H. pylori. In vivo tests further showed that it has good biosafety and virtually no adverse effect on intestinal microflora. Transcriptomics analysis revealed that it kills H. pylori cells mainly by disrupting their cell membranes and metabolism. Additionally, the results of randomized controlled trials on humans disclosed that the oral H. pylori eradication rates achieved by MAXPOWER Biological Antibacterial Liquid were 71.4% and 78.9% according to the intention-to-treat and the per-protocol analysis, respectively. CONCLUSION: MAXPOWER Biological Antibacterial Liquid is both safe and efficacious in the eradication of oral H. pylori. TRIAL REGISTRATION: This study was retrospectively registered in the ClinicalTrials.gov Trial Registry on 21/09/2023 (NCT06045832).

Adsorption of CH4, CO, and H2S on a MoTe2 Monolayer Doped with Metal Atoms (Au and Ru): An Ab Initio Study.

Detecting toxic gases, such as CH4, CO, and H2S, in everyday life holds great significance. This research article focuses on investigating the adsorption characteristics of CH4, CO, and H2S on MoTe2 and MoTe2 doped with Au and Ru using the density functional theory. The study examines various aspects, including adsorption energy, charge transfer, density of states, and charge density difference of the adsorption configuration. The findings demonstrate that the adsorption properties of Ru-doped MoTe2 exhibit a significant enhancement for all three gases, with CO displaying the highest adsorption performance. Through comparative analysis, it is evident that the adsorption affinity between MoTe2-Ru and the three gases is robust, thus indicating improved gas detection capabilities.

Ligand Development for Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Racemic Alkyl Halides.

The enantioconvergent cross-coupling of racemic alkyl halides represents a powerful tool for the synthesis of enantioenriched molecules. In this regard, the first-row transition metal catalysis provides a suitable mechanism for stereoconvergence by converting racemic alkyl halides to prochiral radical intermediates owing to their good single-electron transfer ability. In contrast to the noble development of chiral nickel catalyst, copper-catalyzed enantioconvergent radical cross-coupling of alkyl halides is less studied. Besides the enantiocontrol issue, the major challenge arises from the weak reducing capability of copper that slows the reaction initiation. Recently, significant efforts have been dedicated to basic research aimed at developing chiral ligands for copper-catalyzed enantioconvergent radical cross-coupling of racemic alkyl halides. This perspective will discuss the advances in this burgeoning area with particular emphasis on the strategic chiral anionic ligand design to tune the reducing capability of copper for the reaction initiation under thermal conditions from our research group.

Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines.

α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenriched N-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.

First-principles prediction of layered MoO2and MoOSe as promising cathode materials for magnesium ion batteries.

Magnesium ion battery is one of the promising next-generation energy storage systems. Nevertheless, lack of appropriate cathode materials to ensure massive storage and efficient migration of Mg cations is a big obstacle for development of Mg-ion batteries. Herein, by means of first principles calculations, the geometric structure, electronic structure, Mg intercalation behavior and Mg diffusion behavior of the layered MoO2and two MoOSe (MoOSe(I) and MoOSe(V)) were systematically investigated. Layered MoO2shows semiconductor properties, while MoOSe displays metallic characteristics which ensure higher conductivity. The Mg cations tend to intercalate into octahedral sites for both MoO2and MoOSe. The maximum Mg-storage phases of the layered MoO2, MoOSe(I) and MoOSe(V) correspond to Mg0.666MoO2, Mg0.666MoOSe(I) and Mg0.666MoOSe(V), with theoretical specific capacities of 279, 191 and 191 mAh g-1, respectively. The calculated discharge plateaus of MoO2and two MoOSe are all about 1 V, which ensure that the layered MoO2and MoOSe electrodes can act as cathodes for Mg-ion batteries in the early stage. Moreover, comparing with other cathodes, the diffusion barrier of Mg cations and volume expansion during Mg intercalation process are competitive. The results suggest that layered MoO2and MoOSe are the promising cathode materials for Mg-ion batteries.

[Longitudinal Study of the Association Between Handgrip Strength and Chronic Disease Multimorbidity among Middle-aged and Older Adults].

OBJECTIVE: To investigate the potential association between multimorbidity and the handgrip strength of middle-aged and older adults. METHODS: The baseline (2011) and second-round follow-up (2015) data of China Health and Retirement Longitudinal Study (CHARLS) were used. Adults≥40 were selected as the subjects of the study. Variables incorporated in the study included handgrip strength, chronic disease prevalence, demographic variables, and health behavior variables. Generalized estimating equations were used to analyze the longitudinal association between handgrip strength and multimorbidity. RESULTS: A total of 28 368 middle-aged and older adults were included in the baseline and follow-up samples, with an average age of (59.1±9.7) years old, the oldest being 96 while the youngest being 40. Among them, 6 239 were male, accounting for 47.3%. In the second-round follow-up, 9 186 baseline respondents and 5 994 new respondents were covered, reaching a total of 15 180 respondents. Compared with the baseline, a higher proportion of the second-round follow-up respondents were female ( P=0.033) and were older ( P<0.001). From the baseline to the second-round follow-up, Q1, the lowest grip strength category, increased from 23.4% to 26.6%, while Q4, the highest grip strength category, decreased from 26.5% to 21.2%. The prevalence of having more than three chronic diseases increased from 18.2% to 24.2% and the prevalence of having more than five chronic diseases increased from 3.3% to 6.2%. After adjusting for confounding variables, the interaction items of handgrip strength and time showed statistical significance. After stratification by gender, the interaction items of male handgrip strength and follow-up time were statistically significant in both models ( P<0.05). The marginal effect graph of the interactive item showed that the multimorbidity prevalence of respondents with lower handgrip levels grew faster with age. Individual effect analysis showed that the correlation between handgrip strength and multimorbidity was not statistically significant at baseline, but the follow-up done four years afterwards showed statistical significant correlation between handgrip strength and multimorbidity. CONCLUSION: Respondents with lower baseline handgrip strength are associated with increasingly higher risk of multimorbidity over time. Handgrip strength can be used as an effective screening tool for middle-aged and older adults in China to identify those at higher risks of multimorbidity of chronic diseases.

[A Study of the Relationship Between Job Satisfaction and Work Engagement of Physicians in Public Hospitals].

OBJECTIVE: To understand the level of job satisfaction and work engagement of physicians in public hospitals, to analyze the interaction between job satisfaction and work engagement, and to discuss how each dimension of job satisfaction affects work engagement so as to provide information and reference for improving the level of work engagement of physicians in public hospitals. METHODS: Covering 6 public hospitals in Sichuan (3 tertiary-level hospitals and 3 secondary-level hospitals), 638 questionnaires were obtained from physicians through convenient sampling for data description and analysis. Pearson correlation method was used to analyze the correlation between job satisfaction and work engagement, and multiple linear stepwise regression method was used to analyze work engagement and the influencing factors of each dimension. RESULTS: With regard to job satisfaction, physicians showed high levels of satisfaction in personal safety (3.77±0.87), leadership identification and support (3.59±0.77), and job pressure (3.51±0.81). The mean points of work engagement and each dimension were as follows: total mean points of work engagement (4.02±0.99), dedication (4.21±1.13), absorption (4.19±1.08) and vigor (3.63±1.04). In job satisfaction, salary and benefits, work environment, social recognition, organizational management, leadership identification and support are positively correlated to work engagement and all dimensions. In job satisfaction, 5 dimensions, including social recognition, leadership recognition and support, work achievement, personal safety and organizational management, had a significant influence on work engagement and all dimensions. CONCLUSION: Emphasis on the high-level needs for recognition and self-actualization of doctors, doctor-patient communication, and personal development of doctors may improve doctors' job satisfaction and work engagement.

Copper-Catalyzed Asymmetric Coupling of Allenyl Radicals with Terminal Alkynes to Access Tetrasubstituted Allenes.

In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo-differentiation of remote motifs away from the radical reaction site. We herein describe a copper-catalyzed asymmetric radical 1,4-carboalkynylation of 1,3-enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P-ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3-enynes as well as radical precursors with excellent functional group tolerance.

Copper-Catalyzed Enantioconvergent Radical Suzuki-Miyaura C(sp3)-C(sp2) Cross-Coupling.

A copper-catalyzed enantioconvergent Suzuki-Miyaura C(sp3)-C(sp2) cross-coupling of various racemic alkyl halides with organoboronate esters has been established in high enantioselectivity. Critical to the success is the use of a chiral cinchona alkaloid-derived N,N,P-ligand for not only enhancing the reducing capability of copper catalyst to favor a stereoablative radical pathway over a stereospecific SN2-type process but also providing an ideal chiral environment to achieve the challenging enantiocontrol over the highly reactive radical species. The reaction has a broad scope with respect to both coupling partners, covering aryl- and heteroarylboronate esters, as well as benzyl-, heterobenzyl-, and propargyl bromides and chlorides with good functional group compatibility. Thus, it provides expedient access toward a range of useful enantioenriched skeletons featuring chiral tertiary benzylic stereocenters.

Copper-Catalyzed Asymmetric Radical 1,2-Carboalkynylation of Alkenes with Alkyl Halides and Terminal Alkynes.

A copper-catalyzed intermolecular three-component asymmetric radical 1,2-carboalkynylation of alkenes has been developed, providing straightforward access to diverse chiral alkynes from readily available alkyl halides and terminal alkynes. The utilization of a cinchona alkaloid-derived multidentate N,N,P-ligand is crucial for the efficient radical generation from mildly oxidative precursors by copper and the effective inhibition of the undesired Glaser coupling side reaction. The substrate scope is broad, covering (hetero)aryl-, alkynyl-, and aminocarbonyl-substituted alkenes, (hetero)aryl and alkyl as well as silyl alkynes, and tertiary to primary alkyl radical precursors with excellent functional group compatibility. Facile transformations of the obtained chiral alkynes have also been demonstrated, highlighting the excellent complementarity of this protocol to direct 1,2-dicarbofunctionalization reactions with C(sp2/sp3)-based reagents.

Predictive Value and Correlation of Neuron-Specific Enolase for Prognosis in Patients with Coma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Coma is the most serious disturbance of consciousness, which affects the life quality of patients and increases the burden of their family. Studies to assess the prognostic value of neuron-specific enolase (NSE) in patients with coma have not led to precise, generally accepted prognostic rules. The study aims to assess the correlation between NSE and prognosis of coma and the predictive value of NSE for clinical prognosis. METHODS: A search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data from the establishment time of databases to December 2019. This analysis included patients with coma, regardless of how long the coma was. In total, 26 articles were retrieved and included in the review. RESULTS: The meta-analysis revealed the NSE concentration of patients with coma is significantly higher than that of the control group (standard mean difference = 0.88, 95% confidence interval [CI]: 0.63-1.12, p < 0.05). The pooled sensitivity and specificity of NSE in coma diagnosis was 0.5 (95% CI: 0.39-0.61) and 0.86 (95% CI: 0.71-0.94). CONCLUSIONS: The NSE concentration of patients with poor coma prognosis is significantly higher than that of the control group. The high NSE concentration is not necessarily a poor prognosis for coma, but low NSE concentration indicates a high probability of a good prognosis for coma.

Photoinduced Copper-Catalyzed Asymmetric Decarboxylative Alkynylation with Terminal Alkynes.

We describe a photoinduced copper-catalyzed asymmetric radical decarboxylative alkynylation of bench-stable N-hydroxyphthalimide(NHP)-type esters of racemic alkyl carboxylic acids with terminal alkynes, which provides a flexible platform for the construction of chiral C(sp3 )-C(sp) bonds. Critical to the success of this process are not only the use of the copper catalyst as a dual photo- and cross-coupling catalyst but also tuning of the NHP-type esters to inhibit the facile homodimerization of the alkyl radical and terminal alkyne, respectively. Owing to the use of stable and easily available NHP-type esters, the reaction features a broader substrate scope compared with reactions using the alkyl halide counterparts, covering (hetero)benzyl-, allyl-, and aminocarbonyl-substituted carboxylic acid derivatives, and (hetero)aryl and alkyl as well as silyl alkynes, thus providing a vital complementary approach to the previously reported method.

A Copper Catalyst with a Cinchona-Alkaloid-Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes.

A copper-catalyzed asymmetric radical oxytrifluoromethylation of alkenyl oxime and Togni's reagent has been successfully developed, thereby providing straightforward access to CF3 -containing isoxazolines bearing α-tertiary stereocenters with excellent yield and enantioselectivity. The key to success is the rational design of cinchona-alkaloid-based sulfonamides as neutral/anionic hybrid ligands to effectively control the stereochemistry in copper-catalyzed reactions involving free alkyl radical species. The utility of this method is illustrated by efficient transformation of the products into useful chiral CF3 -containing 1,3-aminoalcohols.

Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation of Alkenes with Alcohols.

A conceptually novel strategy with achiral pyridine as the ancillary ligand to stabilize high-valent copper species for the first asymmetric radical oxytrifluoromethylation of alkenes with alcohols under CuI /phosphoric acid dual-catalysis has been developed. The transformation features mild reaction conditions, a remarkably broad substrate scope and excellent functional group tolerance, offering an efficient approach to a wide range of trifluoromethyl-substituted tetrahydrofurans bearing an α-tertiary stereocenter with excellent enantioselectivity. Mechanistic studies support the presumed role of the achiral pyridine as a coordinative ligand on copper metal to stabilize the key transient reaction species involved in the asymmetric induction process.

Analysis on curative effects and safety of 2% liranaftate ointment in treating tinea pedis and tinea corporis & cruris.

The paper is intended to analyze and evaluate the specific curative effect and safety of 2% liranaftate ointment in treating patients with tinea pedis and tinea cruris. 1,100 cases of patients with tinea pedis and tinea corporis & cruris were selected as research objects and were divided into two groups according to the random number table method. They were treated with different methods: 550 cases of patients were treated with 2% liranaftate ointment for external use in the observation group and the rest 550 cases of patients were treated with 1% bifonazole cream in the control group. The treatment time was two weeks for patients with tinea corporis & cruris and four weeks for those with tinea pedis respectively. Meanwhile, the one-month follow-up visit was conducted among the patients to compare the curative effects of two groups. After the medication, the curative effectiveness rate was 87.65% (482/550) in the observation group, while that was 84.91% (467/550) in the control group. After the average follow-up visits of (15.5±2.4), the curative effectiveness rate 96.55% (531/550) in the observation group, while that was 91.45% (503/550) in the control group. Two groups of patients recovered well with a low incidence of adverse reactions in the treatment, and the overall curative effect was good with the inter-group difference at P>0.05, so it was without statistical significance. The curative effect of 2% liranaftate ointment is safe and obvious in treating tinea pedis and tinea corporis & cruris, so it is valuable for clinical popularization and application.

A Dual-Catalytic Strategy To Direct Asymmetric Radical Aminotrifluoromethylation of Alkenes.

A novel asymmetric radical aminotrifluoromethylation of alkenes has been developed for the first time, providing straightforward access to densely functionalized CF3-containing azaheterocycles bearing an α-tertiary stereocenter with excellent enantioselectivity. The key to success is not only the introduction of a Cu(I)/chiral phosphoric acid dual-catalytic system but also the use of urea with two acidic N-H as both the nucleophile and directing group. The utility of this method is illustrated by facile transformations of the products into other important compounds useful in organic synthesis and medicinal chemistry.

Trigeminal nerve electrical stimulation attenuates early traumatic brain injury through the TLR4/NF-κB/NLRP3 signaling pathway mediated by orexin-A/OX1R system.

BACKGROUND: Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and emerging evidence indicates that trigeminal nerve electrical stimulation (TNS) is a promising therapeutic intervention for neurological impairment following TBI. However, the precise mechanisms underlying the neuroprotective effects of TNS in TBI are poorly understood. Thus, the objective of this study was to investigate the potential involvement of the orexin-A (OX-A)/orexin receptor 1 (OX1R) mediated TLR4/NF-κB/NLRP3 signaling pathway in the neuroprotective effects of TNS in rats with TBI. METHODS: Sprague-Dawley rats were randomly assigned to four groups: sham, TBI, TBI+TNS+SB334867, and TBI+TNS. TBI was induced using a modified Feeney's method, and subsequent behavioral assessments were conducted to evaluate neurological function. The trigeminal nerve trunk was isolated, and TNS was administered following the establishment of the TBI model. The levels of neuroinflammation, brain tissue damage, and proteins associated with the OX1R/TLR4/NF-κB/NLRP3 signaling pathway were assessed using hematoxylin-eosin staining, Nissl staining, western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence techniques. RESULTS: The findings of our study indicate that TNS effectively mitigated tissue damage, reduced brain edema, and alleviated neurological deficits in rats with TBI. Furthermore, TNS demonstrated the ability to attenuate neuroinflammation levels and inhibit the expression of proteins associated with the TLR4/NF-κB/NLRP3 signaling pathway. However, it is important to note that the aforementioned effects of TNS were reversible upon intracerebroventricular injection of an OX1R antagonist. CONCLUSION: TNS may prevent brain damage and relieve neurological deficits after a TBI by inhibiting inflammation, possibly via the TLR4/NF-κB/NLRP3 signaling pathway mediated by OX-A/OX1R.

Cognition-Enhancement Effect of Median Nerve Electrical Stimulation in Patients with Cognitive Impairment: A Retrospective Cohort Study.

OBJECTIVE: People with cognitive impairment often face quality-of-life problems and require ongoing support, which has profound consequences for caregivers and society. Noninvasive brain stimulation techniques, such as median nerve electrical stimulation (MNS), have shown promising potentials in improving cognitive ability in patients with cognitive impairment. Therefore, we aimed to investigate the positive effect and safety of MNS in cognitive impairment. METHODS: Patients diagnosed with cognitive impairment from the hospital record management system of the First Affiliated Hospital of Nanchang University from April 1, 2020, to December 31, 2022, were enrolled. Data on patients' basic characteristics, treatment records, and examination results such as the Mini-Mental State Examination (MMSE), activities of daily living (ADL), and P300 event-related potentials before and after treatment were collected. RESULTS: Overall, 146 patients with cognitive impairment were enrolled, including 71 patients who underwent conventional therapy (standard treatment group) and 75 patients who underwent conventional therapy and MNS operation (active MNS group). Before treatment, there were no differences between the standard treatment and active MNS groups in terms of age, sex, etiology, duration of symptoms before therapy, hospital stay, whether they had undergone surgery, MMSE score, ADL score, and amplitude and latency of the P300 event-related potentials (P > 0.05). After treatment, we observed significant improvements in the MMSE score, ADL score, amplitude of P300, and decreased latency of P300 event-related potentials in both groups compared with before treatment (P < 0.05). In addition, we observed that the active MNS group showed higher MMSE and ADL scores, higher amplitude of P300 event-related potentials, and lower latency of P300 event-related potentials than the standard treatment group after treatment (P < 0.05). Furthermore, no side effects were associated with MNS operation. CONCLUSIONS: These preliminary data provide early evidence that MNS may be a positive effect and safe method for promoting the recovery of cognitive ability in patients with cognitive impairment.

Orexin-A alleviates ferroptosis by activating the Nrf2/HO-1 signaling pathway in traumatic brain injury.

BACKGROUND: Traumatic Brain Injury (TBI) has high disability and mortality rate. Oxidative stress and ferroptosis are important pathophysiological characteristics after TBI. Orexin-A (OXA) can alleviate neuronal damage in diverse neurological disorders. Nevertheless, the role and mechanism of OXA in TBI stay unknown. OBJECTIVES: The research investigated protection influence of OXA on TBI and its potential mechanisms. METHODS: Male Sprague-Dawley rats were randomly grouped into: sham, TBI, TBI + normal saline (NS) and TBI+OXA groups. TBI model was constructed in rat via modified Feeney's approach, and OXA treatment was administered following construction of TBI model. RESULTS: Relative to TBI+NS group, TBI+OXA group displayed greatly recovered tissue damage and neurological deficits. Additionally, OXA eased oxidative stress as well as ferroptosis in cerebral cortex of rats following TBI. Furthermore, OXA increased Nrf2 expression and regulating factors HO-1 and NQO1 in cerebral cortex of TBI rats. CONCLUSIONS: Our research found OXA may restrain ferroptosis via Nrf2/HO-1 signaling pathway activation, thereby reducing brain injury after TBI.