RefMetaPlant: a reference metabolome database for plants across five major phyla.

Plants are unique with tremendous chemical diversity and metabolic complexity, which is highlighted by estimates that green plants collectively produce metabolites numbering in the millions. Plant metabolites play crucial roles in all aspects of plant biology, like growth, development, stress responses, etc. However, the lack of a reference metabolome for plants, and paucity of high-quality standard compound spectral libraries and related analytical tools, have hindered the discovery and functional study of phytochemicals in plants. Here, by leveraging an advanced LC-MS platform, we generated untargeted mass spectral data from >150 plant species collected across the five major phyla. Using a self-developed computation protocol, we constructed reference metabolome for 153 plant species. A 'Reference Metabolome Database for Plants' (RefMetaPlant) was built to encompass the reference metabolome, integrated standard compound mass spectral libraries for annotation, and related query and analytical tools like 'LC-MS/MS Query', 'RefMetaBlast' and 'CompoundLibBlast' for searches and profiling of plant metabolome and metabolite identification. Analogous to a reference genome in genomic research, RefMetaPlant provides a powerful platform to support plant genome-scale metabolite analysis to promote knowledge/data sharing and collaboration in the field of metabolomics. RefMetaPlant is freely available at https://www.biosino.org/RefMetaDB/.

CropMetabolome: a comprehensive metabolome database for major crops cross eight categories.

Chemical compositions of crops are of great agronomical importance, as crops serve as resources for nutrition, energy, and medicines for human and livestock. For crop metabolomics research, the lack of crop reference metabolome and high-quality reference compound mass spectra, as well as utilities for metabolic profiling, has hindered the discovery and functional study of phytochemicals in crops. To meet these challenging needs, we have developed the Crop Metabolome database (abbreviated as CropMetabolome) that is dedicated to the construction of crop reference metabolome, repository, and dissemination of crop metabolomic data, and profiling and analytic tools for metabolomics research. CropMetabolome contains a metabolomics database for more than 50 crops (belonging to eight categories) that integrated self-generated raw mass spectral data and public-source datasets. The reference metabolome for 59 crop species was constructed, which have functions that parallel those of reference genome in genomic studies. CropMetabolome also contains 'Standard compound mass spectral library', 'Flavonoids library', 'Pesticide library', and a set of related analytical tools that enable metabolic profiling based on a reference metabolome (CropRefMetaBlast), annotation and identification of new metabolites (CompoundLibBlast), deducing the structure of novel flavonoid derivatives (FlavoDiscover), and detecting possible residual pesticides in crop samples (PesticiDiscover). In addition, CropMetabolome is a repository to share and disseminate metabolomics data and a platform to promote collaborations to develop reference metabolome for more crop species. CropMetabolome is a comprehensive platform that offers important functions in crop metabolomics research and contributes to improve crop breeding, nutrition, and safety. CropMetabolome is freely available at https://www.cropmetabolome.com/.

HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage.

Damage-associated molecular pattern molecules (DAMPs) play a critical role in mediating cochlear cell death, which leads to noise-induced hearing loss (NIHL). High-mobility group box 1 (HMGB1), a prototypical DAMP released from cells, has been extensively studied in the context of various diseases. However, whether extracellular HMGB1 contributes to cochlear pathogenesis in NIHL and the potential signals initiating HMGB1 release from cochlear cells are not well understood. Here, through the transfection of the adeno-associated virus with HMGB1-HA-tag, we first investigated early cytoplasmic accumulation of HMGB1 in cochlear hair cells after noise exposure. We found that the cochlear administration of HMGB1-neutralizing antibody immediately after noise exposure significantly alleviated hearing loss and outer hair cells (OHCs) death induced by noise exposure. In addition, activation of signal transducer and activators of transcription 1 (STAT1) and cellular hyperacetylation were verified as potential canonical initiators of HMGB1 cytoplasmic accumulation. These findings reveal the adverse effects of extracellular HMGB1 on the cochlea and the potential signaling events mediating HMGB1 release in hair cells, indicating multiple potential pharmacotherapeutic targets for NIHL.

Identification and fine mapping of qPBR10-1, a novel locus controlling panicle blast resistance in Pigm-containing P/TGMS line.

Rice blast is one of the most widespread and devastating diseases in rice production. Tremendous success has been achieved in the identification and characterization of genes and quantitative trait loci (QTLs) conferring seedling blast resistance, however, genetic studies on panicle blast resistance have lagged far behind. In this study, two advanced backcross inbred sister lines (MSJ13 and MSJ18) were obtained in the process of introducing Pigm into C134S and showed significant differences in the panicle blast resistance. One F2 population derived from the crossing MSJ13/MSJ18 was used to QTL mapping for panicle blast resistance using genotyping by sequencing (GBS) method. A total of seven QTLs were identified, including a major QTL qPBR10-1 on chromosome 10 that explains 24.21% of phenotypic variance with LOD scores of 6.62. Furthermore, qPBR10-1 was verified using the BC1F2 and BC1F3 population and narrowed to a 60.6-kb region with six candidate genes predicted, including two genes encoding exonuclease family protein, two genes encoding hypothetical protein, and two genes encoding transposon protein. The nucleotide variations and the expression patterns of the candidate genes were identified and analyzed between MSJ13 and MSJ18 through sequence comparison and RT-PCR approach, and results indicated that ORF1 and ORF2 encoding exonuclease family protein might be the causal candidate genes for panicle blast resistance in the qPBR10-1 locus. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01268-3.

Genetic dissection of grain water content and dehydration rate related to mechanical harvest in maize.

BACKGROUND: The low grain water content (GWC) at harvest is a prerequisite to mechanical harvesting in maize, or otherwise would cause massive broken kernels and increase drying costs. The GWC at harvest in turn depends on GWC at the physiological maturity (PM) stage and grain dehydration rate (GDR). Both GWC and GDR are very complex traits, governed by multiple quantitative trait loci (QTL) and easily influenced by environmental conditions. So far, a number of experiments have been conducted to reveal numbers of GWC and GDR QTL, however, very few QTL have been confirmed, and no QTL has been fine-mapped or even been cloned. RESULTS: We demonstrated that GWCs after PM were positively correlated with GWC at PM, whereas negatively with GDRs after PM. With a recombinant inbred line (RIL) population, we identified totally 31 QTL related to GWC and 17 QTL related to GDR in three field trials. Seven GWC QTL were consistently detected in at least two of the three field trials, each of which could explain 6.92-24.78% of the total GWC variation. Similarly, one GDR QTL was consistently detected, accounting for 9.44-14.46% of the total GDR variation. Three major GWC QTL were found to overlap with three GDR QTL in bins 1.05/06, 2.06/07, and 3.05, respectively. One of the consistent GWC QTL, namely qGwc1.1, was fine-mapped from a 27.22 Mb to a 2.05 Mb region by using recombinant-derived progeny test. The qGwc1.1 acted in a semi-dominant manner to reduce GWC by 1.49-3.31%. CONCLUSIONS: A number of consistent GWC and GDR QTL have been identified, and one of them, QTL-qGwc1.1, was successfully refined into a 2.05 Mb region. Hence, it is realistic to clone the genes underlying the GWC and GDR QTL and to make use of them in breeding of maize varieties with low GWC at harvest.

Ploidy effect and genetic architecture exploration of stalk traits using DH and its corresponding haploid populations in maize.

BACKGROUND: Doubled haploid (DH) lines produced via in vivo haploid induction have become indispensable in maize research and practical breeding, so it is important to understand traits characteristics in DH and its corresponding haploids which derived from each DH lines. In this study, a DH population derived from Zheng58 × Chang7-2 and a haploid population, were developed, genotyped and evaluated to investigate genetic architecture of eight stalk traits, especially rind penetrometer resistance (RPR) and in vitro dry matter digestion (IVDMD), which affecting maize stalk lodging-resistance and feeding values, respectively. RESULTS: Phenotypic correlation coefficients ranged from 0.38 to 0.69 between the two populations for eight stalk traits. Heritability values of all stalk traits ranged from 0.49 to 0.81 in the DH population, and 0.58 to 0.89 in the haploid population. Quantitative trait loci (QTL) mapping study showed that a total of 47 QTL for all traits accounting for genetic variations ranging from 1.6 to 36.5% were detected in two populations. One or more QTL sharing common region for each trait were detected between two different ploidy populations. Potential candidate genes predicated from the four QTL support intervals for RPR and IVDMD were indirectly or directly involved with cellulose and lignin biosynthesis, which participated in cell wall formation. The increased expression levels of lignin and cellulose synthesis key genes in the haploid situation illustrated that dosage compensation may account for genome dosage effect in our study. CONCLUSIONS: The current investigation extended understanding about the genetic basis of stalk traits and correlations between DH and its haploid populations, which showed consistence and difference between them in phenotype, QTL characters, and gene expression. The higher heritabilities and partly higher QTL detection power were presented in haploid population than in DH population. All of which described above could lay a preliminary foundation for genetic architecture study with haploid population and may benefit selection in haploid-stage to reduce cost in DH breeding.

CRISPR-Cas9-mediated editing of the OsHPPD 3' UTR confers enhanced resistance to HPPD-inhibiting herbicides in rice.

This study reports the creation of herbicide-resistant rice lines via CRISPR-Cas9-mediated editing of the 3' UTR of OsHPPD. Resistance index calculations revealed that two resistant lines, TS8-2#-10 and TS8-8#-6, exhibited 4.8-fold and 3.7-fold greater resistance to HPPD-inhibiting herbicides compared with the wild type, YG3012.

Pijx confers broad-spectrum seedling and panicle blast resistance by promoting the degradation of ATP ß subunit and OsRbohC-mediated ROS burst in rice.

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most important diseases of rice. Utilization of blast-resistance genes is the most economical, effective, and environmentally friendly way to control the disease. However, genetic resources with broad-spectrum resistance (BSR) that is effective throughout the rice growth period are rare. In this work, using a genome-wide association study, we identify a new blast-resistance gene, Pijx, which encodes a typical CC-NBS-LRR protein. Pijx is derived from a wild rice species and confers BSR to M. oryzae at both the seedling and panicle stages. The functions of the resistant haplotypes of Pijx are confirmed by gene knockout and overexpression experiments. Mechanistically, the LRR domain in Pijx interacts with and promotes the degradation of the ATP synthase ß subunit (ATPb) via the 26S proteasome pathway. ATPb acts as a negative regulator of Pijx-mediated panicle blast resistance, and interacts with OsRbohC to promote its degradation. Consistently, loss of ATPb function causes an increase in NAPDH content and ROS burst. Remarkably, when Pijx is introgressed into two japonica rice varieties, the introgression lines show BSR and increased yields that are approximately 51.59% and 79.31% higher compared with those of their parents in a natural blast disease nursery. In addition, we generate PPLPijx Pigm and PPLPijx Piz-t pyramided lines and these lines also have higher BSR to panicle blast compared with Pigm- or Piz-t-containing rice plants. Collectively, this study demonstrates that Pijx not only confers BSR to M. oryzae but also maintains high and stable rice yield, providing new genetic resources and molecular targets for breeding rice varieties with broad-spectrum blast resistance.

Prevalence of blindness and low vision: a study in the rural Heilongjiang Province of China.

BACKGROUND: The prevalence of blind individuals in the north of China is unknown. The study aimed to investigate the prevalence and causes of blindness and low vision in rural areas in Heilongjiang province of China in 2008-2009. DESIGN: Cross-sectional study. PARTICIPANTS OR SAMPLES: A cluster random sampling method was used to recruit participants of all ages in rural areas of Heilongjiang. METHODS: Trained professionals performed interviews and clinical examinations to measure visual acuity. The relationships between blindness or low vision and age, gender and education level were analysed. MAIN OUTCOME MEASURES: The main outcome measure was prevalence rates of bilateral blindness and bilateral low vision. RESULTS: Of the 11 787 subjects, 10 384 (88.1%) were surveyed. The overall age-adjusted prevalence rates were 0.7% (95% confidence interval: 0.5-0.8%) for bilateral blindness and 1.7% (95% confidence interval: 1.4-1.9%) for bilateral low vision. The prevalence rates of blindness and low vision were higher in the elderly and uneducated population (P < 0.05). The main causes for blindness and low vision were cataracts (44.1 and 46.0%, respectively) and refractive errors (17.7 and 42.5%, respectively). CONCLUSION: Blindness and low vision are highly prevalent among people with cataracts and refractive errors. Eye care planning must focus on treating the avoidable and curable forms of blindness.

Language reorganization patterns in global aphasia-evidence from fNIRS.

Background: Exploring the brain reorganization patterns associated with language recovery would promote the treatment of global aphasia. While functional near-infrared spectroscopy (fNIRS) has been widely used in the study of speech and language impairment, its application in the field of global aphasia is still limited. Aims: We aimed to identify cortical activation patterns of patients with global aphasia during naming and repetition tasks. Methods and procedures: We recruited patients with post-stroke aphasia from the Department of Rehabilitation Medicine at Huashan Hospital. These individuals were diagnosed with global aphasia without cognitive impairments, as assessed by speech-language pathology evaluations. Age- and sex-matched healthy controls were recruited from the greater Shanghai area. During fNIRS measurement, patients and healthy controls completed the picture-naming and phrase repetition task. Cortical activation patterns on each of these language tasks were then compared between groups. Outcomes and results: A total of nine patients with global aphasia and 14 healthy controls were included in this study. Compared with the healthy subjects, patients with global aphasia showed increased activation in the left Broca's area, middle temporal gyrus (MTG), superior temporal gyrus (STG), and pre-motor and supplementary motor cortex (SMA) (p < 0.05) in the picture-naming task. Furthermore, the latency of the oxyhemoglobin (HbO) concentration in the left supramarginal gyrus (SMG) region had a strong negative correlation with their score of the naming task (p < 0.01). In the phrase repetition task, decreased activation was detected in the left SMA and SMG (p < 0.05) of patients relative to controls. Conclusion: The left SMG plays a critical role in the language function of patients with global aphasia, especially in their abilities to name and repeat. fNIRS is a promising approach to revealing the changes in brain activities in patients with aphasia, and we believe it will contribute to a deeper understanding of the neurological mechanisms and the establishment of a novel treatment approach for global aphasia.

Substandard starch grain4 may function in amyloplast development by influencing starch and lipid metabolism in rice endosperm.

The amyloplast is a specialized plastid in rice endosperm cells where starch is synthesized and stored as starch granules (SGs). However, little is known about the molecular mechanism underlying amyloplast and SG development. In this study, a novel mutant (c134) demonstrating a floury endosperm with enlarged SGs and amyloplasts was identified. The floury endosperm was caused by rounder, loosely packed SG. Grain-quality profile and expression analysis showed reduced contents of total starch and amylose in the c134 mutant, as well as reduced expression of a number of genes involved in starch biosynthesis. Galactosyldiacylglycerol (GDG) content and fatty acid synthesis play important roles in plastid development, and in the c134 endosperm, an obvious decrease in GDG and various fatty acids was observed, with down-regulated expression of various genes involved in lipid biosynthesis. Furthermore, map-based cloning revealed an amino acid substitution (glycine to aspartic acid) in the substandard starch grain4 (SSG4) protein. The results of this study suggest that SSG4 influences the regulation of starch and lipid metabolism as well as amyloplast development, a finding that is useful for potential genetic improvement of rice grain quality in future starch and lipid breeding and biotechnology.

Genomic insight into balancing high yield, good quality, and blast resistance of japonica rice.

BACKGROUND: Balancing the yield, quality and resistance to disease is a daunting challenge in crop breeding due to the negative relationship among these traits. Large-scale genomic landscape analysis of germplasm resources is considered to be an efficient approach to dissect the genetic basis of the complex traits. Central China is one of the main regions where the japonica rice is produced. However, dozens of high-yield rice varieties in this region still exist with low quality or susceptibility to blast disease, severely limiting their application in rice production. RESULTS: Here, we re-sequence 200 japonica rice varieties grown in central China over the past 30 years and analyze the genetic structure of these cultivars using 2.4 million polymorphic SNP markers. Genome-wide association mapping and selection scans indicate that strong selection for high-yield and taste quality associated with low-amylose content may have led to the loss of resistance to the rice blast fungus Magnaporthe oryzae. By extensive bioinformatic analyses of yield components, resistance to rice blast, and taste quality, we identify several superior alleles for these traits in the population. Based on this information, we successfully introduce excellent taste quality and blast-resistant alleles into the background of two high-yield cultivars and develop two elite lines, XY99 and JXY1, with excellent taste, high yield, and broad-spectrum of blast resistance. CONCLUSIONS: This is the first large-scale genomic landscape analysis of japonica rice varieties grown in central China and we demonstrate a balancing of multiple agronomic traits by genomic-based strategy.

[Expression of mutation type GJA8 gene and wild type GJA8 gene of a congenital inherited nuclear cataract family in eukaryotic cells].

OBJECTIVE: To clone the sequence of mutation type GJA8 gene (mGJA8) and wild type GJA8 gene (wGJA8) of a congenital inherited nuclear cataract family and study their expression in eukaryotic cell lines in vitro. METHODS: The mGJA8 and wGJA8 were amplified from this family's DNA and healthy people's DNA by PCR respectively. The mGJA8 and wGJA8 were recombined with plasmid pEGFP-N1 respectively. The accuracy of pEGFP-N1-GJA8 was confirmed by restriction enzyme digestion and DNA sequencing. Finally pEGFP-N1- mGJA8 and pEGFP-N1- wGJA8 and GFP protein were transfected into COS7 cells by lipofectin. The expression of pEGFP-N1-GJA8 and GFP fusion protein were to observe under fluorescence microscope, and to detect by Western-blotting and immunohistochemical staining. RESULTS: The mGJA8 and wGJA8 were cloned successfully. With restricting enzyme digestion analysis and DNA sequencing, recombinant plasmid pEGFP-N1-mGJA8 and pEGFP-N1-wGJA8 were constructed correctly and their GFP fusions were expressed in transfected COS7 cells. The expression of pEGFP-N1-mGJA8 and pEGFP-N1-wGJA8 fusion protein were observed under fluorescence microscope, and detected by Western-blotting and immunohistochemical staining successfully. CONCLUSIONS: The mGJA8 gene and wGJA8 gene are cloned successfully, and pEGFP-N1-mGJA8 and pEGFP-N1-mGJA8 fusion protein can be expressed in COS7 cells, which establish the foundation for further studying the mechanism of this congenital inherited nuclear cataract family.

Association of cytochrome P450 2C19 polymorphisms with coronary heart disease risk: A protocol for systematic review and meta analysis.

BACKGROUND: Polymorphisms in the cytochrome P450 2C19 (CYP2C19) gene have been reported to be associated with coronary heart disease (CHD), but the results were not consistently analyzed among different patient groups. To derive a more precise estimation of these associations, we will conduct a meta-analysis to investigate the polymorphisms of CYP2C19 in all published studies. METHODS: Electronic databases (Google Scholar, ISI Web of Science, Pubmed, Embase, China National Knowledge Infrastructure, Wanfang, and China Biological Medicine) will be used to search clinical case-control or cohort studies about CYP2C19 polymorphism and CHD published until November 2020. Two reviewers will independently select the study, extract the data, and evaluate the quality of the study. Odds ratios with 95% confidence interval will be used to evaluate the strength of the association between the CYP2C19 polymorphism and CHD susceptibility under 4 genetic models. Subgroup analysis will be conducted by different ethnicity and genotyping method. Sensitivity analysis will be performed via sequentially omitting each of the included studies 1 at a time. Begg funnel plots and Egger test will be used to examine the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0. RESULTS: This study will provide a better understanding of the association between CYP2C19 polymorphisms and coronary heart disease risk. CONCLUSION: The publication of this protocol will minimize the possibility of bias due to post hoc changes to the analysis protocol, thus helping to obtain reliable evidence. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/R7U93.

A helitron-induced RabGDIα variant causes quantitative recessive resistance to maize rough dwarf disease.

Maize rough dwarf disease (MRDD), caused by various species of the genus Fijivirus, threatens maize production worldwide. We previously identified a quantitative locus qMrdd1 conferring recessive resistance to one causal species, rice black-streaked dwarf virus (RBSDV). Here, we show that Rab GDP dissociation inhibitor alpha (RabGDIα) is the host susceptibility factor for RBSDV. The viral P7-1 protein binds tightly to the exon-10 and C-terminal regions of RabGDIα to recruit it for viral infection. Insertion of a helitron transposon into RabGDIα intron 10 creates alternative splicing to replace the wild-type exon 10 with a helitron-derived exon 10. The resultant splicing variant RabGDIα-hel has difficulty being recruited by P7-1, thus leading to quantitative recessive resistance to MRDD. All naturally occurring resistance alleles may have arisen from a recent single helitron insertion event. These resistance alleles are valuable to improve maize resistance to MRDD and potentially to engineer RBSDV resistance in other crops.

Endoscopic transnasal canaliculorhinostomy for refractory common canalicular obstruction with an unidentifiable lacrimal sac.

AIM: To describe the role of endoscopic transnasal canaliculorhinostomy (ETC) in refractory common canalicular obstruction (CCO) associated with an absent or unidentifiable lacrimal sac. METHODS: The records of patients with refractory CCO who underwent ETC at the Eye Hospital of Wenzhou Medical University from October 2007 to December 2016 were retrospectively reviewed. RESULTS: Fifty-six patients (56 eyes) with refractory CCO were recruited into the study. Eight patients were excluded due to the presence of a residual lacrimal sac or failure to complete the follow-up duration. The anatomic and functional success rates were both 85.4% (41/48) at a mean follow-up of 18.6mo. Five cases failed as a result of ostial synechia and two failed because of ostial obstruction by granulation. Postoperative complications included mild nasal bleeding in 5 cases, dried nasal feeling in 8 cases, and olfactory dysfunction in 4 cases. CONCLUSION: Although being surgically challenging, ETC has comparable findings to its external approach counterpart or conjunctivodacryocystorhinostomy (CDCR) with Jones tube. And it may prove to be a novel alternate surgical technique for patients with refractory CCO without identifiable lacrimal sac.

Effect of high glucose concentration on VEGF and PEDF expression in cultured retinal Müller cells.

To explore the effect of high glucose concentration on the expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in the cultured rat retinal Müller cells. Rat Müller cells were cultured and RT-PCR and Western-blot analysis were used to measure the levels of VEGF and PEDF in cultured Müller cells at different high glucose concentrations. Under 10, 20, 30 mmol/L high glucose conditions, the levels of VEGF mRNA and protein increased and the levels of PEDF mRNA and protein decreased. These results suggest that the VEGF and PEDF expression in Müller cells are unbalance under high glucose concentration, which contribute to retinal neovascularization in diabetic retinopathy.

Case report repairing orbital skin defects using composite flaps after giant eyelid-derived tumor excision and orbital exenteration.

RATIONALE: Though giant malignant tumors arising in the eyelid are rare, they often require extensive surgery for removal along with orbital exenteration. Because of this, repairing orbital defects is an important factor in the surgical strategy. PATIENT CONCERNS: Case 1 was a 78-year-old nomad man who presented in the Department of Ophthalmology with a giant tumor in his right eyelid, which had developed over three years. Clinical examination revealed a huge pigmented, nonhealing ulcerated lesion, approximately 52×44×40 mm in size. Case 2 was a 52-year old rural male complaining of a huge tumor in the right eyelid. Patient medical history revealed that the mass was initially the size of a soybean and gradually grew over 3 years to the size of a fist. DIAGNOSES: Histopathological examination of the tumors revealed that one was a basal cell carcinoma and the other a sebaceous gland carcinoma. INTERVENTIONS: The two cases of giant malignant eyelid tumors were surgically excised using rapid frozen section margin control. Different pedicle myocutaneous flaps were used to repair the orbital skin defects. OUTCOMES: Postoperative follow-up showed perfect healing of the pedicle flaps and good patient compliance. The results of these cases indicate that covering exposed orbital cavities with composite pedicle mycuaneous flaps is a simple and practical strategy for orbital reconstruction. Not only does this help maintain orbital stability, but it also provides opportunities for patients to return to normal lives. LESSONS: Although surgical management is often the first option for treatment of giant eyelid tumors, recurrence and mortality due to the tumors is still high after long-term follow-up. Therefore, early discovery and treatment is the best way to control the progression of giant eyelid tumors and enhance survivability.

Lactate promotes resistance to glucose starvation via upregulation of Bcl-2 mediated by mTOR activation.

Solid tumors grow faster and need more glucose than normal tissue; however, due to poor angiogenesis and excessive growth, tumors remote from blood vessels are always under glucose starvation. Even so, cancer cells remain alive in vivo. Thus, making cancer cells sensitive to glucose depletion may potentially provide an effective strategy for cancer intervention. Tumors that obtain sufficient glucose generate a large amount of lactate. Therefore, we proposed that lactate, a tumor microenvironment factor, may allow cancer cells to develop resistance to glucose starvation-induced death. We cultured cancer cells in no-glucose medium and added lactate to the medium. During the experiment, lactate helped cancer cells to escape from glucose starvation-induced cell death, without using lactate as an energy substrate, resulting in activation of Akt through PI3K. Akt activation plays a central role in cell growth through the activation of mammalian target of rapamycin (mTOR). Alteration of the PI3K/Akt/mTOR signaling pathway by inhibiting apoptosis induced specific upregulation of B-cell lymphoma 2 (Bcl-2) through translational control. In conclusion, this study showed that lactate rescues cancer cells from glucose starvation-induced cell death through regulation of the PI3K/Akt/mTOR/Bcl-2 signaling pathway. These data suggest that lactate is an important determinant of the sensitivity of tumors to glucose starvation, and reducing lactate or inhibiting the PI3K/Akt/mTOR/Bcl-2 signaling pathway may influence the response of cancers to glucose starvation.