Brown sugar as a carbon source can make agricultural organic waste compost enter the secondary thermophilic stage and promote compost decomposition.

To enhance the efficiency of composting agricultural organic waste (AOW), this study aimed to examine the impact of inoculating tomato straw compost with two distinct microbial agents: ZymoZone (ZZ), a composite microbial agent derived from the straw compost and Effective Microorganisms (EM), a commercial microbial agent. Furthermore, in order to reactivate the microorganisms within the compost during the initial high temperature phase, 10% brown sugar was introduced as a carbon source. The objective of this addition was to assess its influence on the composting process. The findings revealed that compared to the control (CK) group, the ZZ and EM treatments extended the first high-temperature phase by 2 and 1 day, respectively. Furthermore, with the addition of 10% brown sugar, the ZZ and EM treatments remained in the second high-temperature phase for 8 and 7 days, respectively, while the CK treatment had already entered the cooling stage by then. Notably, the inoculation of microbial agents and the addition of brown sugar substantially augmented the activity of lignocellulose-related hydrolases, thereby promoting the degradation of lignocellulose in the ZZ and EM treatment groups. This was confirmed by FTIR analysis, which demonstrated that the addition of microbial agents facilitated the degradation of specific substances, leading to reduced absorbance in the corresponding spectra. XRD analysis further indicated a notable reduction in cellulose crystallinity for both the ZZ (8.00%) and EM (7.73%) treatments. Hence, the incorporation of microbial agents and brown sugar in tomato straw compost effectively enhances the composting process and improves the quality of compost products.

Nanozyme-based inulin@nanogold for adhesive and antibacterial agent with enhanced biosafety.

Nanozymes with oxidase or peroxidase-mimicking activity have emerged as a promising alternative for disinfecting resistant pathogens. However, further research and clinical applications of nanozymes are hampered by their low in vivo biosafety and biocompatibility. In this study, inulin-confined gold nanoparticles (IN@AuNP) are synthesized as an antibacterial agent via a straightforward in situ reduction of Au3+ ions by the hydroxyl groups in inulin. The IN@AuNP exhibits both peroxidase-mimicking and oxidase-mimicking catalytic activities, of which the maximum reaction velocity (Vmax) for H2O2 is 2.66 times higher than that of horseradish peroxidase. IN@AuNP can catalyze the production of reactive oxygen species (ROS), resulting in effective antibacterial behavior against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Abundant hydroxyl groups retained in inulin endow the nanozyme with high adhesion to bacteria, reducing the distance between the captured bacteria and ROS, achieving an antibacterial ratio of 100 % within 1 h. Importantly, due to the natural biosafety and non-absorption of the dietary fiber inulin, as well as the inability of inulin-trapped AuNP to diffuse, the IN@AuNP exhibits high biosafety and biocompatibility under physiological conditions. This work is expected to open a new avenue for nanozymes with great clinical application value.

Efficient enumeration and visualization of helix-coil ensembles.

Helix-coil models are routinely used to interpret circular dichroism data of helical peptides or predict the helicity of naturally-occurring and designed polypeptides. However, a helix-coil model contains significantly more information than mean helicity alone, as it defines the entire ensemble-the equilibrium population of every possible helix-coil configuration-for a given sequence. Many desirable quantities of this ensemble are either not obtained as ensemble averages or are not available using standard helicity-averaging calculations. Enumeration of the entire ensemble can allow calculation of a wider set of ensemble properties, but the exponential size of the configuration space typically renders this intractable. We present an algorithm that efficiently approximates the helix-coil ensemble to arbitrary accuracy by sequentially generating a list of the M highest populated configurations in descending order of population. Truncating this list of (configuration, population) pairs at a desired accuracy provides an approximating sub-ensemble. We demonstrate several uses of this approach for providing insight into helix-coil ensembles and folding mechanisms, including landscape visualization.

Efficient Enumeration and Visualization of Helix-coil Ensembles.

Helix-coil models are routinely used to interpret CD data of helical peptides or predict the helicity of naturally-occurring and designed polypeptides. However, a helix-coil model contains significantly more information than mean helicity alone, as it defines the entire ensemble - the equilibrium population of every possible helix-coil configuration - for a given sequence. Many desirable quantities of this ensemble are either not obtained as ensemble averages, or are not available using standard helicity-averaging calculations. Enumeration of the entire ensemble can allow calculation of a wider set of ensemble properties, but the exponential size of the configuration space typically renders this intractable. We present an algorithm that efficiently approximates the helix-coil ensemble to arbitrary accuracy, by sequentially generating a list of the M highest populated configurations in descending order of population. Truncating this list of (configuration, population) pairs at a desired accuracy provides an approximating sub-ensemble. We demonstrate several uses of this approach for providing insight into helix-coil ensembles and folding mechanisms, including landscape visualization.

Glutathione S-Transferase Highly Expressed in Holotrichia parallela Antennae Inactivates the Odorant Unsaturated Aldehyde Volatiles.

Odorant-degrading enzymes in insects play a vital role in maintaining olfactory sensitivity. However, the role and molecular mechanism of glutathione S-transferases (GSTs) in odorant inactivation has been rarely studied. In the present study, 31 GSTs were identified from the antennal transcriptome of Holotrichia parallela. HpGSTd1 possesses the highest transcriptome expression level. Recombinant HpGSTd1 showed degradation activity toward various unsaturated aldehyde volatiles. Furthermore, the metabolite of cinnamaldehyde was identified by high-resolution mass spectrometry (HRMS). The molecular docking analysis and site-directed mutagenesis revealed the key residues of HpGSTd1 in degrading odorants. In addition, the unsaturated aldehyde volatiles elicited the behavioral and electrophysiological responses of H. parallela. Taken together, our findings suggest that HpGSTd1 may play an essential role in inactivating odorants in H. parallela, which provides new insights for identifying molecular targets and exploring effective olfactory regulators for this underground pest.

Response of Odorant Receptors with Phenylacetaldehyde and the Effects on the Behavior of the Rice Water Weevil (Lissorhoptrus oryzophilus).

The rice water weevil (RWW), Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a destructive rice pest that threatens the rice industry worldwide. Odorant receptors (ORs) and odorant receptor coreceptors (Orcos) play an important role in the process of insects' whole life activities; however, there are no related functional studies on RWW. On this basis, a heterologous study of LoryOR20/LoryOrco in Xenopus laevis oocytes was performed to detect the effects of certain natural compounds on RWWs and four active compounds were found. Electroantennogram (EAG) recordings and a behavior test showed that RWWs exhibited a significant response to phenylacetaldehyde (PAA) and an EAG measurement of dsRNA-LoryOR20-treated RWWs revealed a significant decrease in response to PAA. Our results revealed an olfactory molecular mechanism for the recognition of PAA by RWWs, thus providing a potential genetic target at the peripheral olfactory sensing level, contributing to the development of novel control strategies for pest management.

1-nonene plays an important role in the response of maize-aphid-ladybird tritrophic interactions to nitrogen.

Plant volatile organic compounds (VOCs) are the key distress signals involved in tritrophic interactions, by which plants recruit predators to protect themselves from herbivores. However, the effect of nitrogen fertilization on VOCs that mediate tritrophic interactions remains largely unidentified. In this study, a maize (Zea mays)-aphid (Rhopalosiphum padi)-ladybird (Harmonia axyridis) tritrophic interaction model was constructed under high-nitrogen (HN) and low-nitrogen (LN) regimens. H. axyridis had a stronger tendency to be attracted by aphid-infested maize under HN conditions. Then, volatiles were collected and identified from maize leaves on which aphids had fed. All of the HN-induced volatiles (HNIVs) elicited an electroantennogram (EAG) response from H. axyridis. Of these HNIVs, 1-nonene was attractive to H. axyridis under simulated natural volatilization. Furthermore, our regression showed that the release of 1-nonene was positively correlated with H. axyridis visitation rates. Supplying 1-nonene to maize on which aphids had fed under LN enhanced attractiveness to H. axyridis. These results supported the conclusion that 1-nonene was the active compound that mediated the response to nitrogen in the tritrophic interaction. In addition, the 1-nonene synthesis pathway was hypothesized, and we found that the release of 1-nonene might be related to the presence of salicylic acid (SA) and abscisic acid (ABA). This research contributes to the development of novel environmentally friendly strategies to optimize nitrogen fertilizer application and to improve pest control in maize crops.

Trends in Congenital Insensitivity to Pain with Anhidrosis: A Bibliometric Analysis from 2000 to 2021.

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare inherited autosomal recessive disease that has multiple clinical manifestations. Since its symptoms are related to different systems, this disorder has been investigated on a variety of topics. To better understand publications about CIPA, we conducted a bibliometric study to evaluate research publications on CIPA from 2000 to 2021, and delineate the key contributions in terms of countries, authors and sources. Methods: Quantitative analysis of publications on CIPA from 2000 to 2021 was interpreted and graphed through the Science Citation Index Expanded (SCIE) of Web of Science (WOS) Core Collection. The bibliometric package in R 4.1.1, VOSviewer 1.6.18, and GraphPad Prism 8.4 were used to conduct the bibliometric analysis. Results: From 2000 to 2021, a total of 163 publications were retrieved. China had the largest number of publications (n = 31), while Japan had the highest number of citations (621 citations). Levy J and Indo Y were perhaps the most impactful researchers in the field of CIPA. The co-authorship of authors and institutions indicated little cooperation on CIPA research between different countries. Annals of Neurology (n=5) and Nature Genetics (120 citations) were the most productive and cited journals, respectively, and the top 10 local cited references clarified the theoretical basis of the CIPA research area. Furthermore, the important topics on CIPA mainly include NTRK1 mutations and nerve growth factor (NGF). Conclusion: Based on the bibliometric analysis, we have a comprehensive view of the global status of CIPA research, and the results indicate that CIPA needs more attention and cooperation to facilitate the study of its pathological mechanisms.

Risk assessment of novel coronavirus COVID-19 outbreaks in the border areas of southwest China.

This study aimed to assess the risk of coronavirus disease 2019 in the border areas of southwest China, so as to provide guidance to targeted prevention and control measures in the border areas of different risk levels. We assessed the dependence of the risk of an outbreak in the southwest China from imported cases on key parameters such as the cumulative number of infectious diseases in the border area of southwest China in the past 3 years; the connectivity of the neighboring countries with China's Southwest border, including baseline travel numbers, travel frequencies, the effect of travel restrictions, and the length of borders with neighboring countries; the cumulative number of close contacts of coronavirus disease 2019 patients; (iv) the population density in border areas; the efficacy of control measures in border areas; experts estimated risks in border areas based on experience and then given a score; Spearman correlation and Logistic regression models were used to analyze the associated factors of novel coronavirus. According to the correlation of various factors, we assigned values to each parameter, calculated the risk score of each county, and then divided each county into high, medium, and low risk according to the sick score and took different control measure according to different risk levels. Finally, the total risk level was evaluated according to the Harvard disease risk index model. The number of infectious diseases in the past 3 years, travel numbers, travel frequencies, experts estimated risk score, effect of travel restrictions, and the number of close contacts were associated with the incidence of new coronary pneumonia. It is concluded that bilateral transportation convenience is a risk factor for new coronary pneumonia, (odds ratio = 9.23, 95% confidence interval, 1.99-42.73); the number of observers is a risk factor for new coronary pneumonia (odds ratio = 1.04, 95% confidence interval, 1.00-1.08). We found that in countries with travel numbers, travel frequencies, and experts' estimated risk scores were the influencing factors of novel coronavirus. The effect of travel restrictions and the cumulative number of close contacts of the case are risk factors for novel coronavirus.

Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study.

BACKGROUND: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. METHODS: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. FINDINGS: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. INTERPRETATION: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. FUNDING: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

The herbivore-induced plant volatile tetradecane enhances plant resistance to Holotrichia parallela larvae in maize roots.

BACKGROUND: Many herbivore-induced volatiles have been proven to act as signaling compounds to regulate nearby plant defense responses. However, the precise roles of key volatiles produced by maize roots after Holotrichia parallela larva feeding remain largely unknown. RESULTS: We investigated changes in phytohormones and volatiles in maize roots after H. parallela larval infestation. Marked increases in the phytohormone jasmonic acid (JA) and the volatiles jasmone and tetradecane were induced by herbivores, whereas the salicylic acid content decreased. In addition, pre-exposure to tetradecane markedly increased the levels of the stress hormone JA, its precursors and derivatives, and related gene expression. In addition, pre-exposure altered the production of defensive benzoxazinoid secondary metabolites, resulting in increased plant resistance to H. parallela larvae. Plants pre-exposed to jasmone did not differ from control plants. In addition, bioassays showed that H. parallela larval growth was suppressed by feeding maize roots after pre-exposure to tetradecane. CONCLUSION: These results demonstrate that tetradecane may function as a potent defense induction signal that prepares neighboring plants for incoming attacks. © 2021 Society of Chemical Industry.

Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis.

Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela.

Etiological and epidemiological features of acute respiratory infections in China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

Exploring Residents' Purchase Intention of Green Housings in China: An Extended Perspective of Perceived Value.

The promotion of green housings (GHs) is considered a potentially effective way to save energy, reduce air pollution, and promote industrial upgrading. However, the low level of public acceptance of GHs leads to insufficient GH market penetration in China. Thus, it is significant to explore GH purchase decisions to understand and enhance the market demand for GHs effectively. From an extended perspective of perceived value, this study proposes a comprehensive research model that integrates residents' perceptions and personal traits to examine the influencing mechanism of residents' intention to purchase GHs. The proposed model is empirically tested using data collected from 728 urban residents in China. The results reveal that perceived value is a crucial predictor of GH purchase intention. All dimensions of perceived benefits-including perceived functional benefits, perceived emotional benefits, perceived green benefits, and perceived social benefits-have a positive influence on perceived value, while perceived performance risks have a negative influence on perceived value. Two types of personal traits, namely, environmental concern and social trust, significantly affect residents' perceived benefits and perceived risks. The findings contribute to a more in-depth analysis of the effects of residents' perceptions and personal traits on GH purchase behavior. Furthermore, suggestions for policymakers and developers on popularizing GHs are proposed.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Identification and Enzymatic Activity Evaluation of a Novel CYP2C9 Allelic Variant Discovered in a Patient.

Warfarin is a widely prescribed anticoagulant but the doses required to attain the optimum therapeutic effect exhibit dramatic inter-individual variability. Pharmacogenomics-guided warfarin dosing has been recommended to improve safety and effectiveness. We analyzed the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes among 120 patients taking warfarin. A new coding variant was identified by sequencing CYP2C9. The novel A > G mutation at nucleotide position 14,277 led to an amino acid substitution of isoleucine with valine at position 213 (I213V). The functional consequence of the variant was subsequently evaluated in vitro. cDNA of the novel variant was constructed by site-directed mutagenesis and the recombinant protein was expressed in vitro using a baculovirus-insect cell expression system. The recombinant protein expression was quantified at apoprotein and holoprotein levels. Its enzymatic activities toward tolbutamide, warfarin and losartan were then assessed. It exhibited changed apparent Km values and increases of 148%, 84% and 67% in the intrinsic clearance of tolbutamide, warfarin and losartan, respectively, compared to wild-type CYP2C9*1, indicating dramatically enhanced in vitro enzymatic activity. Our study suggests that the amino acid at position 213 in wild-type CYP2C9*1 may be important for the enzymatic activity of CYP2C9 toward tolbutamide, warfarin and losartan. In summary, a patient taking high-dose warfarin (6.0 mg/day) in order to achieve the target international normalized ratio was found to have a mutation in the CYP2C9 gene.

Quantitative proteomics suggests changes in the carbohydrate metabolism of maize in response to larvae of the belowground herbivore Holotrichia parallela.

The larvae of Holotrichia parallela, a destructive belowground herbivore, may cause yield losses of up to 20% in maize in a typical year. To understand the protein-level mechanisms governing the response of maize to this herbivore, tandem mass tag (TMT) quantitative proteomics was used for the comparative analysis of protein abundance in the maize roots after H. parallela larval attack. A total of 351 upregulated proteins and 303 downregulated proteins were identified. Pathway enrichment analysis revealed that the differentially abundant proteins (DAPs) were most strongly associated with carbohydrate and energy metabolism pathways, such as glycolysis, pentose phosphate pathway and fructose and mannose metabolism. Most glycolysis-related proteins were significantly induced. In addition, H. parallela larval attack decreased the glucose concentrations in the roots. This study demonstrates that maize can manipulate carbohydrate metabolism by modifying glycolysis and pentose phosphate pathway response to root-feeding herbivorous attackers. The results of this study may help to establish a foundation for further functional studies of key protein-mediated responses to H. parallela larvae in maize.

Transcriptome analysis of maize reveals potential key genes involved in the response to belowground herbivore Holotrichia parallela larvae feeding.

The larvae of Holotrichia parallela, a destructive belowground herbivore, causes tremendous damages to maize plants. However, little is known if there are any defense mechanisms in maize roots to defend themselves against this herbivore. In the current research, we carried out RNA-sequencing to investigate the changes in gene transcription level in maize roots after H. parallela larvae infestation. A total of 644 up-regulated genes and 474 down-regulated genes was found. In addition, Gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Weighted gene co-expression network analysis (WGCNA) indicated that peroxidase genes may be the hub genes that regulate maize defenses to H. parallela larvae attack. We also found 105 transcription factors, 44 hormone-related genes, and 62 secondary metabolism-related genes within differentially expressed genes (DEGs). Furthermore, the expression profiles of 12 DEGs from the transcriptome analysis were confirmed by quantitative real-time PCR experiments. This transcriptome analysis provides insights into the molecular mechanisms of the underground defense in maize roots to H. parallela larvae attack and will help to select target genes of maize for defense against belowground herbivory.

Lead-Mediated Highly Diastereoselective Allylation of Aldehydes with Cyclic Allylic Halides.

Lead was found to efficiently mediate the allylation reactions of carbonyl compounds with cyclic allylic halides in the presence of stoichiometric amounts of lithium chloride and a catalytic amount of GaCl3 (20 mol %), leading to the desired homoallylic alcohols in modest to high yields with excellent diastereocontrol (>99:1 syn/anti) and good functional group tolerance. In contrast, the use of either 2-pyridinecarboxaldehyde as the carbonyl substrate or ( E)-cinnamyl bromide as the allylating agent produced the corresponding product with reversed diastereoselectivity (>99:1 anti/syn).

Alpha-lipoic acid protects against cadmium-induced neuronal injury by inhibiting the endoplasmic reticulum stress eIF2α-ATF4 pathway in rat cortical neurons in vitro and in vivo.

The heavy metal cadmium (Cd) is well known to be neurotoxic. Studies have shown that apoptosis plays an essential role in Cd-induced brain injury; however, the mechanisms underlying this injury accompanied by apoptosis have yet to be elucidated. The endoplasmic reticulum (ER) stress plays a key part in the regulation of apoptosis. ER stress is defined as accumulation of unfolded or misfolded proteins in the ER. Here, we demonstrated the role of ER stress on Cd-evoked apoptosis in neuronal cells, as well as the neuroprotective effects of the antioxidant alpha-lipoic acid (α-LA) on Cd-induced ER stress and neuronal injury. In vitro, we observed that Cd activated ER associated proteins via the eIF2α-ATF4 pathway in primary rat cerebral cortical neurons. Furthermore, the ER-stress inhibitor salubrinal blocked the dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and significantly reduced the induction of ER stress marker CHOP, the increase of the B-cell lymphoma-2 associate X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, and apoptosis induced by Cd. In addition, Z-ATAD-FMK (a caspase-12 inhibitor) counteracted the Cd-induced activation of caspase-12 and -3, and apoptosis. These in vitro results collectively suggested that ER stress was required for Cd-induced neuronal apoptosis. Importantly, α-LA inhibited the activation of the ER stress eIF2α-ATF4 pathway, the increase of the Bax/Bcl-2 ratio, the activation of caspase-12 and -3, and the apoptosis induced by Cd. In vivo, we also found that the administration of α-LA alleviated Cd-induced neuronal injury, inhibited the activation of the ER stress eIF2α-ATF4 pathway, restored the Bax/Bcl-2 ratio, and prevented the activation of caspase-12 and -3. Taken together, our results demonstrated that Cd triggered protein changes in the ER accompanied by apoptosis via the eIF2α-ATF4 signaling pathway in the neuronal cells of rats, both in vitro and in vivo. Furthermore, we demonstrated for the first time that α-LA protected neurons from Cd-induced injury partly by inhibiting ER stress in rat cerebral cortical neurons.