Effects of hyperbaric oxygen combined cabin ventilator on critically ill patients with liberation difficulty after tracheostomy.

BACKGROUND: Critically ill patients undergoing liberation often encounter various physiological and clinical complexities and challenges. However, whether the combination of hyperbaric oxygen and in-cabin ventilator therapy could offer a comprehensive approach that may simultaneously address respiratory and potentially improve outcomes in this challenging patient population remain unclear. METHODS: This retrospective study involved 148 patients experiencing difficulty in liberation after tracheotomy. Inclusion criteria comprised ongoing mechanical ventilation need, lung inflammation on computed tomography (CT) scans, and Glasgow Coma Scale (GCS) scores of ≤ 9. Exclusion criteria excluded patients with active bleeding, untreated pneumothorax, cerebrospinal fluid leakage, and a heart rate below 50 beats per minute. Following exclusions, 111 cases were treated with hyperbaric oxygen combined cabin ventilator, of which 72 cases were successfully liberated (SL group) and 28 cases (NSL group) were not successfully liberated. The hyperbaric oxygen chamber group received pressurization to 0.20 MPa (2.0 ATA) for 20 min, followed by 60 min of ventilator oxygen inhalation. Successful liberation was determined by a strict process, including subjective and objective criteria, with a prolonged spontaneous breathing trial. GCS assessments were conducted to evaluate consciousness levels, with scores categorized as normal, mildly impaired, moderately impaired, or severely impaired. RESULTS: Patients who underwent treatment exhibited improved GCS, blood gas indicators, and cardiac function indexes. The improvement of GCS, partial pressure of oxygen (PaO2), oxygen saturation of blood (SaO2), oxygenation index (OI) in the SL group was significantly higher than that of the NSL group. However, there was no significant difference in the improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and stroke volume (SV) between the SL group and the NSL group after treatment. CONCLUSIONS: Hyperbaric oxygen combined with in-cabin ventilator therapy effectively enhances respiratory function, cardiopulmonary function, and various indicators of critically ill patients with liberation difficulty after tracheostomy.

Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study.

BACKGROUND: The relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive. To examine the association of serum testosterone and estradiol concentrations with cognitive function in older men with or without vascular risk factors (VRFs). METHODS: This cross-sectional study consisted of 224 community-dwelling men aged 65-90 years in the Songjiang District of Shanghai, China. Serum testosterone and estradiol were measured by electrochemiluminescence immunoassay. The following five factors were defined as VRFs in this study: obesity, history of hypertension, diabetes, stroke, and coronary heart disease. Multivariable linear regression was used to examine the association of testosterone and estradiol with the Mini-Mental State Examination (MMSE) in participants with or without VRF. Restricted cubic spline (RCS) regression was performed to account for the nonlinearity of these associations. RESULTS: An inverted "U" shaped non-linear relationship was found between testosterone concentration and MMSE score in men with one VRF (P overall =.003, non-linear P =.002). Estradiol showed an inverted "U" shaped non-linear relationship with MMSE score independent of VRFs (men without VRF, P overall =.049, non-linear P =.015; men with one VRF, overall P =.007, non-linear P =.003; men with two or more VRFs, overall P =.009, non-linear P =.005). CONCLUSION: In older men, an optimal level of sex steroid concentration may be beneficial to cognitive function and the VRFs should be considered when interpreting the relationship between sex steroid and cognitive function.

A cohort study of self-perception of ageing and all-cause mortality among older adults in China: a multiple mediators analysis.

BACKGROUND: Positive self-perception of aging (SPA) is a well-known predictor of longevity, while how and to what extent SPA is linked with all-cause mortality among older adults is still unclear. This study aims to elucidate the relationship between positive SPA and all-cause mortality and its potential mediators among Chinese older adults. METHODS: This is a 20-year dynamic cohort study conducted among 22,957 older adults aged ≥ 65 years old from a nationally representative sample. Positive SPA was measured using a validated 7-item scale. Potential mediators including health behaviors and social participation were collected using a self-reported questionnaire. Cox proportional hazards regression models were conducted to examine the association between positive SPA and all-cause mortality. A mediation analysis was conducted to determine whether health behaviors and social participation mediated the association between SPA and all-cause mortality. RESULTS: Throughout follow-up (median [interquartile range], 46 [21-84] months), all-cause mortality was 87.4%. Compared with older adults with the lowest quartile positive SPA, hazard ratio(HR) of all-cause mortality among older adults with the second, third, and fourth quartile of positive SPA was 0.96(95%CI:0.93-1.00), 0.93(95%CI:0.90-0.99), and 0.92(95%CI:0.87-0.96) respectively after controlling for all potential mediators and covariates. The mediation analysis showed that regular daily vegetable intake, physical activity, and high social participation explained 41.1-48.5% of the variance in the association between positive SPA and all-cause mortality. CONCLUSIONS: In this cohort study, we found that high positive SPA was associated with decreased all-cause mortality directly, and indirectly through healthy lifestyle behaviors and social participation. These findings suggest that interventions targeted at promoting or maintaining positive SPA may contribute to healthy ageing among older adults in China.

Life expectancy among older adults with or without frailty in China: multistate modelling of a national longitudinal cohort study.

BACKGROUND: Little is known about life expectancy (LE) with or without frailty. We aimed to estimate the total LE and duration of the state of frailty in China. METHODS: This study included older adults aged 65 years and older from the Chinese Longitudinal Healthy Longevity Study (CLHLS). Frailty status was classified into robust, pre-frailty and frailty based on a cumulative deficit model. Total and specific frailty state LEs at 65 years of age were estimated and stratified by demographic characteristics, behaviours, and psychosocial factors using continuous-time multistate modelling. RESULTS: The total LE of older adults aged 65 years in China was 14.74 years on average (95% CI: 14.52-14.94), of which 4.18 years (95% CI: 4.05-4.30) were robust, 7.46 years (95% CI: 7.31-7.61) pre-frail and 3.10 years (95% CI: 3.01-3.20) frail. Older adults with higher robust LE included men (4.71 years, 95% CI: 4.56-4.88), married older adults (4.41 years, 95% CI: 4.27-4.56), those engaging in physical activity (4.41 years, 95% CI: 4.23-4.59), those consuming fruits daily (4.48 years, 95% CI: 4.22-4.77) and those with high social participation (4.39 years, 95% CI: 4.26-4.53). Increased educational attainment were gradually associated with increased robust LE. CONCLUSIONS: Frailty may lead to a reduced total LE and robust LE of older adults in China. In addition to finding inequalities in total and robust LEs by socioeconomic status, our findings also highlight that healthy behaviours and social participation may ease frailty-related reductions in total and robust LE. Our findings imply that national life-course strategies aimed at frailty screening and psychosocial and behavioural interventions could be important for health aging in China.

Synergy of Cd Doping and S Vacancies in CdxZn1-xIn2S4 Hierarchical Nanotubes for Highly Improved Visible-Light-Driven H2 Evolution.

Photocatalytic water splitting over semiconductors is believed as a promising avenue to obtain H2 fuel from renewable solar energy. However, developing highly active and non-noble-metal photocatalysts for H2 evolution is still quite challenging to date. In this work, by constructing nanosheet-based nanotubes with Cd-doping and S vacancies, a highly improved visible-light-driven H2 production for ZnIn2S4 is achieved. Unlike nanoflowers aggregated with nanosheets, the nanosheet-assembled hierarchical nanotubes allow multiple scattering and reflection of incident light within the interior space, leading to an enhanced light-harvesting efficiency. Together with the benefits from Cd doping and S-vacancy engineering, including narrowed band gaps, efficient transmission and separation of charge carriers, abundant catalytically active sites, heightened photo-stability and photo-electron reduction capacity, as well as a strong electrostatic attraction to protons, the synthesized S-deficient CdxZn1-xIn2S4 hierarchical nanotubes exhibit an extraordinary photocatalytic H2 evolution capability under visible-light irradiation, delivering an outstanding H2-generation activity of 28.99 mmol·g-1·h-1 (corresponding to an apparent quantum yield of 37.1% at 400 nm), which is much superior to that of CdxZn1-xIn2S4 nanoflowers, Pt-loaded ZnIn2S4 nanotubes, and most ever reported ZnIn2S4-based photocatalysts. Our study could inspire the development of low-cost and high-performance photocatalysts via rational structural design and optimization.

Terpenoids from the Sponge Sarcotragus sp. Collected in the South China Sea.

Sarcotragusolides A-D (1-4), four new butenolide sesterterpenes featuring a rare methyl-transferred 6/6/6-tricyclic fused ring system with a butyrolactone moiety, and echinohalimane B (8), an unprecedented monocyclic diterpenoid featuring a 2,7-ring-opened halimane-type skeleton, were isolated from the sponge Sarcotragus sp. A γ-hydroxybutenolide sesterterpene derivative (5), a new scalarane sesterterpene (7), a new subersin-type diterpenoid (10), and two known terpenoids were also isolated and identified. The discovery of sarcotragusolides C and D (3 and 4) with an unprecedented inversion of configuration implied a distinct biosynthetic pathway. The structures of these compounds were elucidated based on their spectroscopic data, single-crystal X-ray diffraction, chemical derivatization, and quantum chemical calculations. Compounds 1a, 1b, and 2 presented modest cytotoxic activities against several human cancer cell lines.

Cytotoxic Manoalide-Type Sesterterpenes from the Sponge Luffariella variabilis Collected in the South China Sea.

Thirteen new linear terpenes, including 11 rare acyclic manoalide derivatives (1-11), one polyprenylphenol derivative (12), and one polyprenylbenzaldehyde derivative (13), together with three known compounds (14-16) were isolated from the sponge Luffariella variabilis collected in the South China Sea. The planar structures were resolved by NMR and MS analyses, while the absolute configurations were fully elucidated by NOESY experiments, combined with experimental and calculated ECD spectra, acetal formation, empirical rules of 1H and 13C NMR shifts, DP4+ probability analyses, and Mosher's method. Compounds 1-7, 10, and 13 demonstrated cytotoxic activities against several human cancer cell lines with IC50 values ranging from 2 to 10 µM.

Mixed lichenoid and psoriasiform drug eruption induced by rifampicin.

Rifampicin is an essential first line anti-tuberculosis drug. However, several cases of adverse reactions associated with this drug have been reported, the most common of which are cutaneous drug reactions. We report a case of mixed lichenoid and psoriasiform drug eruption induced by rifampicin.

Impact of ambient temperature on hospital admissions for cardiovascular disease in Hefei City, China.

Many studies have quantified the hospitalization risk for cardiovascular disease (CVD) caused by temperature, but the results of most studies are not consistent. In this study, we evaluate the effect of temperature on CVD hospitalizations. We use a quasi-Poisson regression with a distributed-lag nonlinear model (DLNM) to evaluate the effect of temperature on CVD hospitalizations between July 1, 2015, and October 31, 2017, in Hefei City, China. We found that the cold effect and heat effect of temperature can impact CVD hospital admissions. Compared with the 25th percentile of temperature (10.3 °C), the cumulative relative risk (RR) of extremely low temperature (first percentile of temperature, 0.075 °C) over lags 0-27 days was 0.616 (95% CI 0.423-0.891), and the cumulative RR of moderate low temperature (10th percentile of temperature, 5.16 °C) was 1.081 (95% CI 1.019-1.147) over lags 0-7 days. Compared with the 75th percentile of temperature (25.6 °C), the cumulative RR of extremely high temperature (99th percentile of temperature, 33.7 °C) was 1.078 (95% CI 0.752-1.547) over lags 0-27 days, and the cumulative RR of moderate-high temperature (90th percentile of temperature, 29.0 °C) was 1.015 (95% CI 0.988-1.043) over lag 0 day. In the subgroup, the < 65-year group and male were more susceptible to low temperature; however, the ≥ 65-year group and female were more vulnerable to high temperature. The high temperature's impact on CVD hospital admissions was found to be more obvious in female and the ≥ 65-year group compared to male and the < 65-year group. However, the < 65-year group and men are more sensitive to low temperature.

Photoinduced bending behavior of cross-linked azobenzene liquid-crystalline polymer films with a poly(oxyethylene) backbone.

Cross-linked azobenzene liquid-crystalline polymer films with a poly(oxyethylene) backbone are synthesized by photoinitiated cationic copolymerization. Azobenzene moieties in the film surface toward the light source are simultaneously photoaligned during photopolymerization with unpolarized 436 nm light and thus form a splayed alignment in the whole film. The prepared films show reversible photoinduced bending behavior with opposite bending directions when different surfaces of one film face to ultraviolet light irradiation.

Correlation between existential form of ruthenium cocatalyst and photocatalytic hydrogen evolution of carbon nitride.

Catalysts composed of nanocluster and single-atom (SA) were extensively used to enhance electrocatalytic water splitting performance, whereas study of their photocatalytic hydrogen (H2) evolution activity was limited. Herein, carbon nitride (CN) decorated by ruthenium (Ru) cocatalysts existed as SA + cluster, cluster + nanoparticles (NPs), and NPs were prepared by impregnation and calcination processes. The correlation between existential form, content of Ru cocatalyst and H2 evolution rate were carefully discussed. It was found that Ru NPs were favor for water molecule adsorption, whereas Ru SAs and clusters facilitated H2 desorption. Theoretical calculations revealed that Ru clusters + NPs cocatalyst were beneficial for H* intermediate formation. Water splitting tests found that 1.07 wt% Ru NPs + cluster modified CN showed the highest H2 evolution rate of 13.64 mmol h-1 g-1, which was 266.4 and 1.5 times higher than those of CN and Ru NPs (2.33 wt%) decorated CN, respectively. This work deeply reveals the influences of existential form of Ru cocatalysts on photocatalytic water splitting of CN, and provides thought in designing new cocatalysts to largely enhance H2 evolution.

Interfacial bonding of Co3O4 and oxygen vacancies engineering on ZnO induced efficient peroxymonosulfate activation and pollutants degradation.

A heterojunction of trace Co3O4 bonded on oxygen vacancies (OVs)-rich ZnO (OVs-ZnO/Co3O4) was synthesized via defect-assisted method to promote peroxymonosulfate (PMS) activation and pollutants degradation. Experiments and theoretical calculations demonstrated that electrons could efficiently transfer from OVs-ZnO to Co3O4. OVs-ZnO and Co3O4 played different roles in activating PMS. PMS was easily adsorbed on the OVs-ZnO to form PMS* complex and mediated electron transfer to oxide ciprofloxacin (CIP), whereas, Co3O4 facilitated breakup of peroxide bond to produce radicals. The optimal OVs-ZnO/Co3O4 with Co content of 1.34% exhibited good PMS decomposition ability (94.2% in 30 min) compared to unmodified ZnO (24.2%), stability and anti-interference feature in removing CIP, 96.9% CIP (10 ppm) and 79.6% of total organic carbon were removed in 30 min. Moreover, the OVs-ZnO/Co3O4 achieved 91.2% CIP removal ratio with 1.0 mM PMS via a flow-through device in 180 min. This study proposes a new strategy to enhance PMS activation of ZnO and provides new viewpoint in PMS activation way.

Introducing Br, K, and cyano group into carbon nitride for efficient photocatalytic hydrogen peroxide production then in situ tetracycline mineralization.

In this work, Br, K-doped and cyano group-rich carbon nitride (CN) were prepared via pyrolysis of molten urea and 6-Bromopyridine-3-carbaldehyde, followed by re-calcination with potassium thiocyanate. The hydrogen peroxide (H2O2) evolution and in situ tetracycline (TC) mineralization performances of the prepared samples were studied. The optimal sample could produce 9127 µmol g-1 h-1 H2O2 from 10 vol% ethanol solution and air atmosphere, which was 10.9 times higher than that of pristine CN. With addition of 4 mg L-1 Fe2+ ions, 97.2% of TC (10 mg L-1) and 98.7% of total organic carbon were removed in 30 min under the actions of holes, hydroxyl and superoxide radicals. The high H2O2 yield and TC mineralization ratio were attributed to the increased light absorption, efficient electrons-holes separation, enhanced surface O2 adsorption (0.3878 mmol g-1), and accelerated conversion from Fe3+ to Fe2+ ions. Meanwhile, the system possessed good reusability in H2O2 evolution and TC removal. It is expected that this work can provide new ideas to design CN-based photo-Fenton system to treat wastewater.

Protection of Proanthocyanidins Against HSP Serum-Induced Inflammation and Oxidative Stress on Human Umbilical Vein Endothelial Cells.

Background: Immune-mediated inflammation and oxidative stress play pivotal roles in Henoch-Schonlein purpura (HSP), primarily through the TLR4/MyD88/NF-κB pathway. Proanthocyanidins (PCs) exert anti-inflammatory and antioxidant effects by regulating some signals like TLR4/MyD88/NF-κB. Previous research uncovered that PCs could alleviate purpura-like lesions and pathological changes on rats likely through attenuating inflammation and OS damage. The mechanism of PCs on HSP deserves further investigation. Objective: To clarify the potential mechanism of PCs to HUVECs induced by the serum of HSP patients. Methods: HUVECs were randomly divided into blank, control, model, and low-, medium-, and high-concentration PCs group. Then, 25% HSP serum was assigned to the latter four groups, while 25% serum from healthy subjects to control group and serum-free culture medium to blank one. The last three groups separately received different concentrations of PCs. In addition, TAK-242, a TLR4 inhibitor, was applied to investigate the effect of TLR4-related signals in PCs against HSP serum-induced damage. Finally, inflammatory and OS-related parameters were detected by using cytological/molecular-biological techniques. Results: Treated with HSP serum later, the levels of immuno-inflammatory and oxidative indicators obviously went up (P < 0.05), and those of antioxidants remarkably went down (P < 0.05). PCs, however, reversed above phenomena (P < 0.05). Moreover, TLR4, MyD88 and NF-κB proteins/genes highly expressed in the model group; but significantly fell off in the presence of PCs (P < 0.05). Amazingly, all of above indicators showed no significant difference among the groups of different PCs concentrations (P > 0.05). These alterations likewise occurred after TAK-242 pretreatment with or without PCs, ie a notable drop of TLR4, MyD88 and NF-κB appeared in TAK-242 presence, few differences existing when compared to the PCs groups. Conclusion: PCs effectively protect HUVECs from inflammatory and OS damage provoked by HSP serum via blocking TLR4/MyD88/NF-κB signals.

Defect-mediated Fermi level modulation boosting photo-activity of spatially-ordered S-scheme heterojunction.

Spatially-ordered S-scheme photocatalysts are intriguing due to their enhanced light harvesting, spatially isolated redox sites, and strong redox abilities. Nonetheless, heightening the performance of S-scheme photocatalysts via controllable defect engineering is still challenging to now. In this work, multi-armed MoSe2/CdS S-scheme heterojunction with intimate Mo-S bond coupling and adjustable Se vacancies (VSe) and Mo5+ concentrations was constructed, which consisted of few- or even single-layered MoSe2 growing on the {11-20} facets of wurtzite CdS arms. The S-scheme charge transmission mechanism of MoSe2/CdS heterojunction was validated by density functional theory calculation combined with in situ photo-irradiated X-ray photoelectron spectroscopy, surface photovoltage, and radical measurements. Moreover, the Fermi level gap between CdS and MoSe2 was enlarged by regulating the contents of donor (VSe) and acceptor (Mo5+) impurities with synthesis temperature, which strengthens the built-in electric field and carriers transfer driving force of MoSe2/CdS composites, contributing to an outstanding H2 evolution activity of 52.62 mmol·g-1·h-1 (corresponding to an apparent quantum efficiency of 34.8 % at 400 nm) under visible-light irradiation (λ > 400 nm), 25.8 times that of Pt-loaded CdS counterpart and a substantial amount of reported CdS-containing photocatalysts. Our study results are anticipated to facilitate the rational design of advanced semiconductor nanostructures for efficient solar conversion and utilization.

Types of Home and Community-Based Physical Activity and Their Effects on the Older Adults' Quality of Life: A Systematic Review and Meta-Analysis.

Home and community-based physical activity (HCBPA) has been extensively utilized among older adults. Nevertheless, the varying types of HCBPA, including different duration, intensity, and frequency, have sparked controversy regarding their impact on the quality of life in older adults. This study aims to explore the effects of HCBPA on QoL in older adults. We conducted a systematic review and retrieved studies published from January 2000 to April 2023 from multiple databases (PubMed, Embase, Cochrane, and the Web of Science Library). Seventeen articles met the inclusion criteria for this study. Long-term HCBPA interventions may have a more pronounced positive impact on older adults' quality of life than short-term ones, with the intervention's intensity and frequency playing a key role in its effectiveness. The results of the meta-analyses showed significant differences in PCS but not in MCS, both with low certainty of evidence. Policymakers should prioritize the importance of promoting HCBPA interventions with appropriate duration, intensity, and frequency to create a more age-inclusive society.

Spatially ordered NiOOH-ZnS/CdS heterostructures with an efficient photo-carrier transmission channel for markedly improved H2 production.

Spatially-ordered 1D nanocrystal-based semiconductor nanostructures possess distinct merits for photocatalytic reaction, including large surface area, fast carrier separation, and enhanced light scattering and absorption. Nevertheless, establishing a valid photo-carrier transmission channel is still crucial yet challenging for semiconductor heterostructures to realize efficient photocatalysis. In this work, spatially ordered NiOOH-ZnS/CdS heterostructures were constructed by sequential ZnS coating and NiOOH photo-deposition on multi-armed CdS, which consists of {112̄0}-faceted wurtzite nanorods grown epitaxially on {111}-faceted zinc blende core. Intriguingly, the surface photovoltage spectroscopy and PbO2 photo-deposition results suggest that the photogenerated holes of CdS were first transferred to the Zn-vacancy level of ZnS and then to NiOOH, as driven by the built-in electric field between ZnS and CdS and the hole-extracting effect of the NiOOH cocatalyst, leading to the efficient charge separation of NiOOH-ZnS/CdS. With visible-light (λ > 420 nm) irradiation, NiOOH-ZnS/CdS exhibited a distinguished H2-evolution rate of 152.20 mmol g-1 h-1 (apparent quantum efficiency of 40.9% at 420 nm), approximately 18 folds that of 3 wt% Pt-loaded CdS and much higher than that of ZnS/CdS and NiOOH-CdS counterparts as well as the most reported CdS-containing photocatalysts. Moreover, the cycling and long-term H2 generation tests manifested the outstanding photocatalyst stability of NiOOH-ZnS/CdS. The study results presented here may propel the controllable design of highly-active nanomaterials for solar conversion and utilization.

Near-unity quantum yield and long-term emission stability in halide perovskite nanocrystal glass composite.

Metal halide perovskites are promising optoelectronic materials due to their outstanding luminescent properties. However, the instability of perovskites has long been the bottleneck to their practical applications. Here Cs4PbBr6 nanocrystals based glass composite (Cs4PbBr6 NCs@glass) are successfully prepared, which displays green emission color (520 nm), narrow bandwidth (23 nm) and a near-unity photoluminescence quantum yield (PLQY). The H2O molecules permeating in the lattice of Cs4PbBr6 were found to be a crucial role in the subband energy emission. The Cs4PbBr6 NCs@glass has excellent emission stability; maintains 93 % of initial PL intensity after ultraviolet light irradiation for over 5000 h. In addition, by adjusting the halogen content, we have achieved tunable emission color from blue (450 nm) to green (520 nm) and red (670 nm) on Cs4PbX6 NCs@glass (X = Cl, Br, I), which covers up to 127 % of the National Television Systems Board (NTSC) standard system. Our finding indicates the commercial applications of perovskite materials in lighting and display.

Adeno-Associated Virus Type 9-Mediated Gene Therapy of Choline Acetyltransferase-Deficient Mice.

The enzyme choline acetyltransferase (ChAT) synthesizes acetylcholine from acetyl-CoA and choline at the neuromuscular junction and at the nerve terminals of cholinergic neurons. Mutations in the ChAT gene (CHAT) result in a presynaptic congenital myasthenic syndrome (CMS) that often associates with life-threatening episodes of apnea. Knockout mice for Chat (Chat-/-) die at birth. To circumvent the lethality of this model, we crossed mutant mice possessing loxP sites flanking Chat exons 4 and 5 with mice that expressed Cre-ERT2. Injection of tamoxifen (Tx) at postnatal (P) day 11 in these mice induced downregulation of Chat, autonomic failure, weakness, and death. However, a proportion of Chatflox/flox-Cre-ERT2 mice receiving at birth an intracerebroventricular injection of 2 × 1013 vg/kg adeno-associated virus type 9 (AAV9) carrying human CHAT (AAV9-CHAT) survived a subsequent Tx injection and lived to adulthood without showing signs of weakness. Likewise, injection of AA9-CHAT by intracisternal injection at P28 after the onset of weakness also resulted in survival to adulthood. The expression of Chat in spinal motor neurons of Chatflox/flox-Cre-ERT2 mice injected with Tx was markedly reduced, but AAV-injected mice showed a robust recovery of ChAT expression, which was mainly translated by the human CHAT RNA. The biodistribution of the viral genome was widespread but maximal in the spinal cord and brain of AAV-injected mice. No significant histopathological changes were observed in the brain, liver, and heart of AAV-injected mice after 1 year follow-up. Thus, AAV9-mediated gene therapy may provide an effective and safe treatment for patients severely affected with CHAT-CMS.