Glycyrrhizic acid inhibits DNA damage repair and enhances cisplatin-induced apoptosis of melanoma cells.

This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 µm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.

Improved specificity and efficacy of base-editing therapies with hybrid guide RNAs.

Phenylketonuria (PKU), hereditary tyrosinemia type 1 (HT1), and mucopolysaccharidosis type 1 (MPSI) are autosomal recessive disorders linked to the phenylalanine hydroxylase (PAH) gene, fumarylacetoacetate hydrolase (FAH) gene, and alpha-L-iduronidase (IDUA) gene, respectively. Potential therapeutic strategies to ameliorate disease include corrective editing of pathogenic variants in the PAH and IDUA genes and, as a variant-agnostic approach, inactivation of the 4-hydroxyphenylpyruvate dioxygenase (HPD) gene, a modifier of HT1, via adenine base editing. Here we evaluated the off-target editing profiles of therapeutic lead guide RNAs (gRNAs) that, when combined with adenine base editors correct the recurrent PAH P281L variant, PAH R408W variant, or IDUA W402X variant or disrupt the HPD gene in human hepatocytes. To mitigate off-target mutagenesis, we systematically screened hybrid gRNAs with DNA nucleotide substitutions. Comprehensive and variant-aware specificity profiling of these hybrid gRNAs reveal dramatically reduced off-target editing and reduced bystander editing. Lastly, in a humanized PAH P281L mouse model, we showed that when formulated in lipid nanoparticles (LNPs) with adenine base editor mRNA, selected hybrid gRNAs revert the PKU phenotype, substantially enhance on-target editing, and reduce bystander editing in vivo. These studies highlight the utility of hybrid gRNAs to improve the safety and efficacy of base-editing therapies.

A base editing strategy using mRNA-LNPs for in vivo correction of the most frequent phenylketonuria variant.

The c.1222C>T (p.Arg408Trp) phenylalanine hydroxylase (PAH) variant is the most frequent cause of phenylketonuria (PKU), an autosomal recessive disorder characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels. Here we devised a therapeutic base editing strategy to correct the variant, using prime-edited hepatocyte cell lines engineered with the c.1222C>T variant to screen a variety of adenine base editors and guide RNAs in vitro, followed by assessment in c.1222C>T humanized mice in vivo. We found that upon delivery of a selected adenine base editor mRNA/guide RNA combination into mice via lipid nanoparticles (LNPs), there was sufficient PAH editing in the liver to fully normalize blood Phe levels within 48 h. This work establishes the viability of a base editing strategy to correct the most common pathogenic variant found in individuals with the most common inborn error of metabolism, albeit with potential limitations compared with other genome editing approaches.

Preliminary comparative genomics analysis among Corynebacterium kroppenstedtii complex necessitates a reassessment of precise species associated with mastitis.

AIMS: This study aimed to characterize the first complete genome of Corynebacterium parakroppenstedtii and clarify the evolutionary relationship in the Corynebacterium kroppenstedtii complex (CKC) by using comparative genomics analysis. METHODS AND RESULTS: The genome of isolate yu01 from a breast specimen was sequenced, and 35 CKC genomes were collected. Analysis of 16S rRNA, rpoB, and fusA suggested ambiguous identification, whereas ANI analysis assigned isolate yu01 as Coryne. parakroppenstedtii. The fourth genospecies "Corynebacterium aliikroppenstedtii" was identified in CKC. Comparative genomics analysis suggested that the genomic arrangement in CKC was highly conserved. A total of 43 potential virulence genes and 79 species-specific genes were detected. Most genome-based phylogenetic analysis were incapable of resolving the interspecific evolutionary relationships among CKCs. A total of 20 core genes were found to be distinguishable in CKC. CONCLUSIONS: This study suggested the limited divergence and unavailability of normal single gene-based identification in CKC and questioned the precise species of strains associated with mastitis, identified as Coryne. kroppenstedtii in previous studies. The 20 genes showed potential to enhance the methods for the identification and epidemiological investigation of CKC.

Efficient in vivo prime editing corrects the most frequent phenylketonuria variant, associated with high unmet medical need.

The c.1222C>T (p.Arg408Trp) variant in the phenylalanine hydroxylase gene (PAH) is the most frequent cause of phenylketonuria (PKU), the most common inborn error of metabolism. This autosomal-recessive disorder is characterized by accumulation of blood phenylalanine (Phe) to neurotoxic levels. Using real-world data, we observed that despite dietary and medical interventions, most PKU individuals harboring at least one c.1222C>T variant experience chronic, severe Phe elevations and do not comply with Phe monitoring guidelines. Motivated by these findings, we generated an edited c.1222C>T hepatocyte cell line and humanized c.1222C>T mouse models, with which we demonstrated efficient in vitro and in vivo correction of the variant with prime editing. Delivery via adeno-associated viral (AAV) vectors reproducibly achieved complete normalization of blood Phe levels in PKU mice, with up to 52% whole-liver corrective PAH editing. These studies validate a strategy involving prime editing as a potential treatment for a large proportion of individuals with PKU.

The optimal time restricted eating interventions for blood pressure, weight, fat mass, glucose, and lipids: A meta-analyses and systematic review.

BACKGROUND: No previous systematic review or meta-analysis has evaluated the effect of optimal time-restricted eating (TRE) interventions on cardiovascular (CVD) risk factors. This meta-analysis aimed to illustrate the effect of a suitable TRE on CVD risk factors. METHODS: A systematic review was performed to identify trials reporting the effects of TRE, relative to non-diet controls, on CVD risk factors in humans. A random-effects model was used to evaluate the effect sizes, and the results are expressed as the mean difference (MD) and 95% confidence intervals (CIs). Subgroup analyses were performed to examine the influence of the study population, age, duration of intervention, and baseline mean BMI on the CVD indexes. RESULTS: TRE intervention significantly reduced systolic pressure (SBP) (MD: -3.45 mmHg; 95%CI:(-6.20,-0.71) mmHg; P = 0.01), body weight (MD: -1.63 Kg; 95%CI:(-2.09,-1.17) Kg; P<0.001), body mass index (BMI) (MD: -0.47 Kg/m2; 95% CI: (-0.72, -0.22) Kg/m2; P<0.001), and fat mass (MD: -0.98 Kg; 95% CI: (-1.51,-0.44) Kg; P<0.001), and reduced blood glucose levels. Based on the results of subgroup analysis, this meta-analysis identified the optimal TRE for BP (with a 6 h feeding window, last eating time point at 6-8 PM, and male participants with obesity and aged ≥ 45 years), obesity (with a 6 h feeding window, last eating time point at 6-8 PM, and female participants aged ≥ 45 years), lipids (with an 8 h feeding window, last eating time point at 6-8 PM, and male participants aged < 45 years), and glucose (with a 10-12 h feeding window, last eating time point before 6 PM, and female participants aged < 45years). CONCLUSIONS: Relative to a non-diet control, TRE is effective for the improvement of CVD risks. Moreover, individual TRE interventions should be developed for different populations to achieve the most effective health improvement for CVD risk factors.

Magnetic-assisted exciton-plasmon interactions modulated Bi2S3 nanorods@MoS2 nanosheets heterojunction: towards a split-type photoelectrochemical sensing of profenofos.

A split-type photoelectrochemical (PEC) sensor was designed for the detection of profenofos (PFF) depending on the magnetic-assisted exciton-plasmon interactions (EPI) between the semiconductor substrate and Au NPs. The core-shell Bi2S3 nanorods@MoS2 nanosheets (Bi2S3 NRs@MoS2 NSs) heterostructure nanomaterial with fascinating performance was synthesized and used as the photovoltaic conversion substrate and signal molecules absorption platform. The PEC sensor is operated by co-incubating with the released Au NPs-cDNA from the surface of magnetic beads, originating from the target-triggered DNA double-stranded structure opening event. Due to the strong EPI effects, the photocurrent of Bi2S3 NRs@MoS2 NSs decreased and varied with the PFF concentrations. The proposed PEC sensor exhibited outstanding analytical performances, including a wide linear range (1.0 pg mL-1~1.0 µg mL-1), low detection limitation (0.23 pg mL-1, at 3 σ/m), excellent specificity, high stability, and applicability. Overall, this work provides a new signal strategy for PEC biosensors and extends its application in environmental analysis.

Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.

DNA methyltransferase type 1 (DNMT1) is a major enzyme involved in maintaining the methylation pattern after DNA replication. Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). We used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to explore the epigenomic and transcriptomic effects of mutations in DNMT1. We show cell type-specific changes in gene expression and DNA methylation patterns. DNA methylation and gene expression changes were negatively correlated in iPSCs and iNs. In addition, we identified a group of genes associated with clinical phenotypes of ADCA-DN, including PDGFB and PRDM8 for cerebellar ataxia, psychosis and dementia and NR2F1 for deafness and optic atrophy. Furthermore, ZFP57, which is required to maintain gene imprinting through DNA methylation during early development, was hypomethylated in promoters and exhibited upregulated expression in patients with ADCA-DN in both iPSC and iNs. Our results provide insight into the functions of DNMT1 and the molecular changes associated with ADCA-DN, with potential implications for genes associated with related phenotypes.

Self-checking dual-modal aptasensor based on hybrid Z-scheme heterostructure of Zn-defective CdS/ZnS for oxytetracycline detection.

Electrochemical detection methods have been widely used for trace target detection with satisfactory results. However, most of the existing electrochemical sensors rely only on single signal output, which inevitably suffer from the interference of the complex matrix of real samples. Herein, we proposed a dual-modal aptasensor for oxytetracycline assay with self-checking function by integrating photoelectrochemical (PEC) and electrochemical (EC) signal outputs in one analysis system. Zn-defective CdS/ZnS heterostructure was synthesized and served as the photo-electroactive substrate for constructing the biorecognition process, while methylene blue (MB) was used as a dual-functional probe to enhance both PEC and EC signals. Due to the high activity of Zn-defective CdS/ZnS heterojunction and the unique dual-modal signal readout strategy, the biosensing platform exhibits superior analytical performance with the relatively wide linear range (0.01-50 ng mL-1), lower detection limits of 1.86 pg mL-1 (PEC mode) and 3.08 pg mL-1 (EC mode), as well as good selectivity, stability and reproducibility. The proposed dual-model analytical system with self-checking function is envisioned to provide a new approach for sensitive and reliable biosensing.

Epigenome Editing Durability Varies Widely Across Cardiovascular Disease Target Genes.

Background: Hepatic knockdown of the proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) gene or the angiopoietin-like 3 ( ANGPTL3 ) gene has been demonstrated to reduce blood low-density lipoprotein cholesterol (LDL-C) levels, and hepatic knockdown of the angiotensinogen ( AGT ) gene has been demonstrated to reduce blood pressure. Genome editing can productively target each of these three genes in hepatocytes in the liver, offering the possibility of durable "one-and-done" therapies for hypercholesterolemia and hypertension. However, concerns around making permanent gene sequence changes via DNA strand breaks might hinder acceptance of these therapies. Epigenome editing offers an alternative approach to gene inactivation, via silencing of gene expression by methylation of the promoter region, but the long-term durability of epigenome editing remains to be established. Methods: We assessed the ability of epigenome editing to durably reduce the expression of the human PCSK9, ANGPTL3 , and AGT genes in HuH-7 hepatoma cells. Using the CRISPRoff epigenome editor, we identified guide RNAs that produced efficient gene knockdown immediately after transfection. We assessed the durability of gene expression and methylation changes through serial cell passages. Results: Cells treated with CRISPRoff and PCSK9 guide RNAs were maintained for up to 124 cell doublings and demonstrated durable knockdown of gene expression and increased CpG dinucleotide methylation in the promoter, exon 1, and intron 1 regions. In contrast, cells treated with CRISPRoff and ANGPTL3 guide RNAs experienced only transient knockdown of gene expression. Cells treated with CRISPRoff and AGT guide RNAs also experienced transient knockdown of gene expression; although initially there was increased CpG methylation throughout the early part of the gene, this methylation was geographically heterogeneous-transient in the promoter, and stable in intron 1. Conclusions: This work demonstrates precise and durable gene regulation via methylation, supporting a new therapeutic approach for protection against cardiovascular disease via knockdown of genes such as PCSK9 . However, the durability of knockdown with methylation changes is not generalizable across target genes, likely limiting the therapeutic potential of epigenome editing compared to other modalities.

Mechanical digit sensory stimulation: a randomized control trial on neurological and motor recovery in acute stroke.

Background: Mechanical digit sensory stimulation (MDSS) is a novel therapy designed to accelerate the recovery of upper limb (including hand) function in patients with hemiplegia following a stroke. The primary goal of this study was to investigate the effect of MDSS on patients with acute ischemic stroke (AIS). Methods: Sixty-one inpatients with AIS were randomly divided into conventional rehabilitation group (RG) and stimulation group (SG), and the latter group received MDSS therapy. A healthy group consisting of 30 healthy adults was also included. The interleukin-17A (IL-17A), vascular endothelial growth factor A (VEGF-A), and tumor necrosis factor-alpha (TNF-α) plasma levels were measured in all subjects. The neurological and motor functions of patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), Fugel-Meyer Assessment (FMA), and Modified Barthel Index (MBI). Results: After 12 days of intervention, the IL-17A, TNF-α, and NIHSS levels were significantly decreased, while the VEGF-A, MMSE, FMA, and MBI levels were significantly increased in both disease groups. No significant difference was observed between both disease groups after intervention. The levels of IL-17A and TNF-α were positively correlated with NIHSS but negatively correlated with MMSE, FMA, and MBI. The VEGF-A levels were negatively correlated with NIHSS but positively correlated with MMSE, FMA, and MBI. Conclusion: Both MDSS and conventional rehabilitation significantly reduce the production of IL-17A and TNF-α, increase the VEGF-A levels, and effectively improve cognition and motor function of hemiplegic patients with AIS, and the effects of MDSS and conventional rehabilitation are comparable.

Rapid and definitive treatment of phenylketonuria in variant-humanized mice with corrective editing.

Phenylketonuria (PKU), an autosomal recessive disorder caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene, results in the accumulation of blood phenylalanine (Phe) to neurotoxic levels. Current dietary and medical treatments are chronic and reduce, rather than normalize, blood Phe levels. Among the most frequently occurring PAH variants in PKU patients is the P281L (c.842C>T) variant. Using a CRISPR prime-edited hepatocyte cell line and a humanized PKU mouse model, we demonstrate efficient in vitro and in vivo correction of the P281L variant with adenine base editing. With the delivery of ABE8.8 mRNA and either of two guide RNAs in vivo using lipid nanoparticles (LNPs) in humanized PKU mice, we observe complete and durable normalization of blood Phe levels within 48 h of treatment, resulting from corrective PAH editing in the liver. These studies nominate a drug candidate for further development as a definitive treatment for a subset of PKU patients.

The policy implemented by the government and the protection effect of PM2.5 decreasing on blood pressure in adolescents: From a quasi-experimental study.

Background: High particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) exposure levels posed a great risk to human health, but the protection effects of environmental protection on cardiovascular disease have not been systematically evaluated. This study aims to illustrate the effect of the decreased concentration of PM2.5 on blood pressure level in adolescents after enacting the protection measures of environment from a cohort study. Methods: A quasi-experimental study including 2415 children from the Chongqing Children's Health Cohort, aged 7.32 ± 0.60 years with normal blood pressure at baseline, with 53.94% males, were analysed. Both the generalised linear regression model (GLM) and Poisson regression model were used to calculate the impact of the declining exposure level of PM2.5 on blood pressure and the incidence of prehypertension and hypertension. Results: The annual mean PM2.5 concentration in 2014 and in 2019 were 65.01 ± 6.46 µgmes per cubic metre (µg / m3), 42.08 ± 2.04 µg / m3 respectively, and the decreased PM2.5 concentration between 2014 and 2019 was 22.92 ± 4.51 µg / m3. The effect of decreased PM2.5 concentration by 1µg / m3 on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and the difference of blood pressure (BP) indexes between 2014 and 2019 were all significant (P < 0.001). The absolute differences of SBP (-3.598 mmHg; 95% confidence interval (CI) = -4.47,-2.72 mm Hg), DBP (-2.052 mmHg; 95% CI = -2.80,-1.31 mm Hg) and MAP (-2.568 mmHg; 95% CI = -3.27,-1.87 mm Hg) in the group with a decreased level of ≥25.56 µg / m3 were more significant than those in a decreased concentration of PM2.5 for <25.56 µg / m3 (P < 0.001). And the incidence of prehypertension and hypertension for three occasions blood pressure diagnose was 2.21% (95% CI = 1.37%-3.05%, P = 0.001) in children with PM2.5 decreased level ≤25.56 µg / m3 (50%), which was significant higher than its' counterparts 0.89% (95% CI = 0.37%-1.42%, P = 0.001). Conclusions: Our study found the etiological relationship between the declining PM2.5 concentration and the BP values and the incidence of prehypertension and hypertension in children and adolescents, suggesting continuous environmental protection measures in China have achieved remarkable health benefits.

Depiction of neuroendocrine features associated with immunotherapy response using a novel one-class predictor in lung adenocarcinoma.

BACKGROUND: Tumours with no evidence of neuroendocrine transformation histologically but harbouring neuroendocrine features are collectively referred to as non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED). Investigating the mechanisms underlying NED is conducive to designing appropriate treatment options for NSCLC patients. METHODS: In the present study, we integrated multiple lung cancer datasets to identify neuroendocrine features using a one-class logistic regression (OCLR) machine learning algorithm trained on small cell lung cancer (SCLC) cells, a pulmonary neuroendocrine cell type, based on the transcriptome of NSCLC and named the NED index (NEDI). Single-sample gene set enrichment analysis, pathway enrichment analysis, ESTIMATE algorithm analysis, and unsupervised subclass mapping (SubMap) were performed to assess the altered pathways and immune characteristics of lung cancer samples with different NEDI values. RESULTS: We developed and validated a novel one-class predictor based on the expression values of 13,279 mRNAs to quantitatively evaluate neuroendocrine features in NSCLC. We observed that a higher NEDI correlated with better prognosis in patients with LUAD. In addition, we observed that a higher NEDI was significantly associated with reduced immune cell infiltration and immune effector molecule expression. Furthermore, we found that etoposide-based chemotherapy might be more effective in the treatment of LUAD with high NEDI values. Moreover, we noted that tumours with low NEDI values had better responses to immunotherapy than those with high NEDI values. CONCLUSIONS: Our findings improve the understanding of NED and provide a useful strategy for applying NEDI-based risk stratification to guide decision-making in the treatment of LUAD.

Bimetallic AuPt alloy/rod-like CeO2 nanojunctions with high peroxidase-like activity for colorimetric sensing of organophosphorus pesticides.

Organophosphorus pesticides (OP) have extensive applications in agriculture, while their overuse causes inevitable residues in food, soil, and water, ultimately being harmful to human health and even causing diverse dysfunctions. Herein, a novel colorimetric platform was established for quantitative determination of malathion based on peroxidase mimic AuPt alloy decorated on CeO2 nanorods (CeO2@AuPt NRs). The synthesized nanozyme oxidized colorless 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. Besides, the oxidized TMB was inversely reduced by ascorbic acid (AA), which were originated from hydrolysis of L-ascorbic acid-2-phosphate (AA2P) with the assistance of acid phosphatase (ACP). Based upon this observation ACP analysis was explored by colorimetry, showing a wid linear range of 0.2 ~ 3.5 U L-1 and a low limit of detection (LOD = 0.085 U L-1, S/N = 3). Furthermore, malathion present in the colorimetric system inhibited the activity of ACP and simultaneously affected the generation of AA, in turn promoting the recovery of the chromogenic reaction. Based on this, the LOD was decreased to 1.5 nM (S/N = 3) for the assay of malathion with a wide linear range of 6 ~ 100 nM. This simple colorimetric platform provides some informative guidelines for determination of other pesticides and disease markers.

[Retracted] MicroRNA­143 inhibits cell migration and invasion by targeting matrix metalloproteinase 13 in prostate cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the panels showing the results from cell migration and invasion assay experiments in Fig. 2 on p. 628 contained sections of data that were overlapping with other panels within the same figure. Given the issue of the overlapping sections of data, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of an overall lack of confidence in the presented results. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 8: 626­630, 2013; DOI: 10.3892/mmr.2013.1501].

Abdominal obesity-related lipid metabolites may mediate the association between obesity and glucose dysregulation.

BACKGROUND: Children with obesity is associated with a higher risk of cardiovascular disease (CV) risk in adulthood. This study is to explore the obesity-related lipid metabolites and identify the associations of lipid metabolites with selected CV risk in children and adolescents. METHODS: A case-control study was designed to include a total of 197 children (aged 9-13 years, male 56.34%, 99 children in the obesity group). The lipidomics profiling was measured by ultra-high-performance liquid tandem chromatography quadrupole time-of-flight mass spectrometry. RESULTS: Four FDR-significant abdominal obesity-related lipid metabolites were identified. Compared to the lean group, decreased phosphatidylcholine O-21:2 level (q = 0.010) and sphingomyelins d21:1 (q = 0.029) were found and two lipid metabolites levels were higher in the obese group, including phosphatidylglycerol 43:6 and one did not match with any candidate compounds in databases. After adjusting for covariates, PC3 (O-21:2) and SM (d21:1) were significantly associated with blood glucose. Mediation analysis showed that all three lipid metabolites may mediate the association between abdominal obesity and glucose regulation. CONCLUSIONS: This study identified several novel central obesity-related lipid metabolites, and we found that PC3 (O-21:2) and SM (d21:1) were significantly associated with blood glucose, and all these lipid metabolites can mediate the association between abdominal obesity and glucose dysregulation. IMPACT: Serum lipidomic profiles in children with abdominal obesity and their associations with selected CV risk factors were examined. Our study identified 4 lipid metabolites associated with abdominal obesity, including PC3 (O-21:2), SM (d21:1), PG (43:6), and one did not match with any candidate compounds in the databases. PC3 (O-21:2) and SM (d21:1) were significantly associated with blood glucose. Mediation analysis showed that all three lipid metabolites [PC3 (O-21:2), SM (d21:1), PG (43:6)] may mediate the association between abdominal obesity and abnormal glucose regulation. This study identified several novel obesity-related lipid metabolites.

Lignocellulose dissociation with biological pretreatment towards the biochemical platform: A review.

Lignocellulose utilization has been gaining great attention worldwide due to its abundance, accessibility, renewability and recyclability. Destruction and dissociation of the cross-linked, hierarchical structure within cellulose hemicellulose and lignin is the key procedure during chemical utilization of lignocellulose. Of the pretreatments, biological treatment, which can effectively target the complex structures, is attractive due to its mild reaction conditions and environmentally friendly characteristics. Herein, we report a comprehensive review of the current biological pretreatments for lignocellulose dissociation and their corresponding degradation mechanisms. Firstly, we analyze the layered, hierarchical structure of cell wall, and the cross-linked network between cellulose, hemicellulose and lignin, then highlight that the cracking of ß-aryl ether is considered the key to lignin degradation because of its dominant position. Secondly, we explore the effect of biological pretreatments, such as fungi, bacteria, microbial consortium, and enzymes, on substrate structure and degradation efficiency. Additionally, combining biological pretreatment with other methods (chemical methods and catalytic materials) may reduce the time necessary for the whole process, which also help to strengthen the lignocellulose dissociation efficiency. Thirdly, we summarize the related applications of lignocellulose, such as fuel production, chemicals platform, and bio-pulping, which could effectively alleviate the energy pressure through bioconversion into high value-added products. Based on reviewing of current progress of lignocellulose pretreatment, the challenges and future prospects are emphasized. Genetic engineering and other technologies to modify strains or enzymes for improved biotransformation efficiency will be the focus of future research.