Identification of volatile biomarkers for lung cancer from different histological sources: A comprehensive study.

The identification of noninvasive volatile biomarkers for lung cancer is a significant clinical challenge. Through in vitro studies, the recognition of altered metabolism in cell volatile organic compound (VOC) emitting profile, along with the occurrence of oncogenesis, provides insight into the biochemical pathways involved in the production and metabolism of lung cancer volatile biomarkers. In this research, for the first time, a comprehensive comparative analysis of the volatile metabolites in NSCLS cells (A549), SCLC cells (H446), lung normal cells (BEAS-2B), as well as metabolites in both the oxidative stress (OS) group and control group. Specifically, the combination of eleven VOCs, including n-dodecane, acetaldehyde, isopropylbenzene, p-ethyltoluene and cis-1,3-dichloropropene, exhibited potential as volatile biomarkers for lung cancer originating from two different histological sources. Furthermore, the screening process in A549 cell lines resulted in the identification of three exclusive biomarkers, isopropylbenzene, formaldehyde and bromoform. Similarly, the exclusive biomarkers 1,2,4-trimethylbenzene, p-ethyltoluene, and cis-1,3-dichloropropene were present in the H446 cell line. Additionally, significant changes in trans-2-pentene, acetaldehyde, 1,2,4-trimethylbenzene, and bromoform were observed, indicating a strong association with OS. These findings highlight the potential of volatile biomarkers profiling as a means of noninvasive identification for lung cancer diagnosis.

Unlocking the potential of Chinese herbal medicine residue-derived biochar as an efficient adsorbent for high-performance tetracycline removal.

This study employed hydrothermal carbonization (HTC) in conjunction with ZnCl2 activation and pyrolysis to produce biochar from one traditional Chinese medicine astragali radix (AR) residue. The resultant biochar was evaluated as a sustainable adsorbent for tetracycline (TC) elimination from water. The adsorption performance of TC on two micropore-rich AR biochars, AR@ZnCl2 (1370 m2 g-1) and HAR@ZnCl2 (1896 m2 g-1), was comprehensively evaluated using adsorption isotherms, kinetics, and thermodynamics. By virtue of pore diffusion, π-π interaction, electrostatic attraction, and hydrogen bonding, the prepared AR biochar showed exceptional adsorption properties for TC. Notably, the maximum adsorption capacity (930.3 mg g-1) of TC on HAR@ZnCl2 can be achieved when the adsorbent dosage is 0.5 g L-1 and C0 is 500 mg L-1 at 323 K. The TC adsorption on HAR@ZnCl2 took place spontaneously. Furthermore, the impact of competitive ions behavior is insignificant when coexisting ion concentrations fall within the 10-100 mg L-1 range. Additionally, the produced biochar illustrated good economic benefits, with a payback of 701 $ t-1. More importantly, even after ten cycles, HAR@ZnCl2 still presented great TC removal efficiency (above 77%), suggesting a good application prosperity. In summary, the effectiveness and sustainability of AR biochar, a biowaste-derived product, were demonstrated in its ability to remove antibiotics from water, showing great potential in wastewater treatment application.

Comprehensive Analysis of Fatty Acid Metabolism in Diabetic Nephropathy from the Perspective of Immune Landscapes, Diagnosis and Precise Therapy.

Objective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated. Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using "ConsensusClusterPlus". DN subtypes-associated modules were discovered by "WGCNA", and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using "CIBERSORT" and "CMAP", respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool "Nephroseq v5" was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers' expression. Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1. Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.

ERRα regulates synaptic transmission through reactive oxygen species in hippocampal neurons.

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor α (ERRα) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERRα on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERRα expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERRα. Additionally, we also found that knocking down ERRα expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERRα knockdown. These results indicate a new possible cellular mechanism by which ERRα affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.

Telbivudine-induced rhabdomyolysis in a patient undergoing haemodialysis: A case report and review of literature.

Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.

Primary Plasmablastic Lymphoma of The Paranasal Sinuses: A Rare Case Report.

Plasmablastic lymphoma (PBL) is a rare and highly invasive type of non-Hodgkin's lymphoma. It is usually associated with immunosuppression and human immunodeficiency virus infection. PBL most commonly occurs in the oral cavity, lymph nodes, and in other extranodal sites. However, it rarely originates from bilateral sinuses. Herein, we report the case of a 59-year-old man diagnosed with primary PBL of the sinuses confirmed by endoscopic biopsy, imaging materials, histopathological examination, and immunohistochemistry. The patient underwent 4 cycles of chemotherapy and 22 rounds of radiation therapy for 8 months. Re-examination by sinus computed tomography revealed no obvious tumor tissue in the nasal cavity and sinuses, suggesting that treatment was effective. No local recurrence or distant metastasis was detected at 6-month follow-up after the end of treatment.

CXCR5 Regulates Neuronal Polarity Development and Migration in the Embryonic Stage via F-Actin Homeostasis and Results in Epilepsy-Related Behavior.

Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy. Subsequently, we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol- and kainic acid-induced seizures, whereas CXCR5 overexpression had the opposite effect. CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons. Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model, we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment. Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability, resulting in an increased number of seizures. Finally, our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism, namely, the disruption of neuronal polarity.

Efficient Eu3+-Integrated UiO-66 Probe for Ratiometric Fluorescence Sensing of Styrene and Cyclohexanone.

The development of probes with sensitive and prompt detection of volatile organic compounds (VOCs) is of great importance for protecting human health and public security. Herein, we successfully prepared a series of bimetallic lanthanide metal-organic framework (Eu/Zr-UiO-66) by incorporating Eu3+ for fluorescence sensing of VOCs (especially styrene and cyclohexanone) using a one-pot method. Based on the multiple fluorescence signal responses of Eu/Zr-UiO-66 toward styrene and cyclohexanone, a ratiometric fluorescence probe using (I617/I320) and (I617/I330) as output signals was developed to recognize styrene and cyclohexanone, respectively. Benefitting from the multiple fluorescence response, the limits of detection (LODs) of Eu/Zr-UiO-66 (1:9) for styrene and cyclohexanone were 1.5 and 2.5 ppm, respectively. These are among the lowest reported levels for MOF-based sensors, and this is the first known material for fluorescence sensing of cyclohexanone. Fluorescence quenching by styrene was mainly owing to the large electronegativity of styrene and fluorescence resonance energy transfer (FRET). However, FRET was accounted for fluorescence quenching by cyclohexanone. Moreover, Eu/Zr-UiO-66 (1:9) exhibited good anti-interference ability and recycling performance for styrene and cyclohexanone. More importantly, the visual recognition of styrene and EB vapor can be directly realized with the naked eyes using Eu/Zr-UiO-66 (1:9) test strips. This strategy provides a sensitive, selective, and reliable method for the visual sensing of styrene and cyclohexanone.

MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription.

Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-d-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. The epileptic behavioural phenotype was alleviated by overexpression of STAT1 which reduced the expression of NMDARs, and by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1-NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target.

Primary nasal tuberculosis: A rare case report.

Nasal primary tuberculosis (TB) of the upper respiratory tract is rare and barely reported in literature. Herein, we report a complicated case of nasal primary TB with otitis media. The patient visited the ENT clinic due to left-side nasal obstruction accompanied by rhinorrhea, and intermittent headaches. The diagnosis of nasal TB was confirmed with an acid-fast bacterial test and histopathological examination. After 3 months of treatment with anti-TB drugs, patient's symptoms of nasal obstruction, rhinorrhea, and other symptoms were remarkably relieved. The left ear purulence substantially reduced. The patient recovered well and had no recurrence post half a year of follow-up. Our case emphasizes the importance of accurate diagnosis and initiation of timely treatment. Additionally, when a patient has nasal TB complicated with otitis media, it is important to consider a diagnosis of middle ear TB.

TMT-based proteomics profile reveals changes of the entorhinal cortex in a kainic acid model of epilepsy in mice.

Experimental modeling and clinical neuroimaging of patients has shown that certain seizures are capable of causing neuronal death. Research into cell death after seizures has identified the induction of the molecular machinery of apoptosis. Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults, which is characterized by substantial pathological abnormalities in the temporal lobe, including the hippocampus and entorhinal cortex (EC). Although decades of studies have revealed numerous molecular abnormalities in the hippocampus that are linked to TLE, the biochemical mechanisms associated with TLE in EC remain unclear. In this study, we explored these early phenotypical alterations in the EC 5 days after mice were given a systemic injection of kainic acid (KA) to induce status epilepticus (KA-SE). we used the Tandem Mass Tag (TMT) combined with LC-MS/MS approach to identify distinct proteins in the EC in a mouse model of KA-SE model. According to the findings, 355 differentially abundant proteins including 199 upregulated and 156 downregulated differentially abundant proteins were discovered. The first-ranked biological process according to Gene Ontology (GO) analysis was "negative control of extrinsic apoptotic signaling". "Apoptosis" was the most significantly enriched Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway. Compared with those in control mice, BCL2L1, NTRK2 and MAPK10 abundance levels were reduced in KA mice. MAPK10 and NTRK2 act as upstream regulators to regulate BCL2L1, and BCL2L1 Inhibits cell death by blocking the voltage- dependent anion channel (VDAC) and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. However, ITPR1 was increased at the mRNA and protein levels in KA mice. Furthermore, there was no significant difference in ACTB, TUBA1A and TUBA4A levels between the two groups. Our results offer clues to help identify biomarkers for the development of pharmacological therapies targeted at epilepsy.

Biochar Derived from Chinese Herb Medicine Residues for Rhodamine B Dye Adsorption.

In this study, one well-known CHM residue (Atropa belladonna L., ABL) was used to prepare biochar capable of adsorbing rhodamine B (RhB) with an ultrahigh surface area for the first time. Three micropore-rich ABL biochars including ABL@ZnCl2 (1866 m2/g), ABL@H3PO4 (1488 m2/g), and ABL@KOH (590 m2/g) were obtained using the one-step carbonization method with activation agents (ZnCl2, H3PO4, and KOH) via chemical activation and carbonization at 500 °C, and their adsorption performance for RhB was systematically studied with adsorption kinetics, isotherms, and thermodynamics. Through pore diffusion, π-π interaction, and hydrogen bonding, ABL biochar had excellent adsorption performance for RhB. Moreover, when C 0 was 200 mg/L, biochar dosage was 1 g/L, and the contact time was 120 min; the maximum RhB adsorption capacity and removal efficiency on ABL@ZnCl2 and ABL@H3PO4 were 190.63 mg/g, 95% and 184.70 mg/g, 92%, respectively, indicating that it was feasible to prepare biochar from the ABL residue for RhB adsorption. The theoretical maximum adsorption capacities of ABL@ZnCl2 and ABL@H3PO4 for RhB were 263.19 mg/g and 309.11 mg/g at 25 °C, respectively. Furthermore, the prepared biochar showed good economic applicability, with pay back of USD 972/t (ABL@ZnCl2) and USD 987/t (ABL@H3PO4), respectively. More importantly, even after five cycles, ABL@H3PO4 biochar still showed great RhB removal efficiency, suggesting that it had a good application prospect and provided a new method for the resource utilization of traditional CHM residues. Additionally, pore diffusion, π-π interactions, and hydrogen bonding all play roles in the physical adsorption of RhB on ABL biochar. π-π interactions dominated in the early stage of RhB adsorption on ABL@H3PO4, while pore diffusion played a crucial role in the whole adsorption process on both adsorbents.

A Soft and Bistable Gripper with Adjustable Energy Barrier for Fast Capture in Space.

Actuators for fast capture are essential in the tasks of space structure assembly and space debris disposal. To avoid damage and rebound caused by collision, the mechanical devices for capture or docking impose very strict restrictions on the collision speed. The gripper made of soft material can realize compliant grasping, but its actuating speed and driving mode should adapt to the scenarios of grasping moving objects in space. By harnessing the rapid occurrence of structural instability and tuning its triggering conditions, we present a soft and bistable gripper for dynamic capture. The gripper deforms on the collision with other objects, and it absorbs the kinetic energy of the objects to trigger an instability, and then achieve fast grasping as well as cushioning. This process does not need any other input energy, and it greatly simplifies the conventional driving devices so as to realize the miniaturized and light-weight gripping actuation. The proper pre-deformation to the bistable structure of the gripper enables one to dynamically adjust the energy barrier for triggering the onset of instability to achieve the optimal grasping and buffering effect according to the kinetic characteristics of targets. After finishing one grasping task, the bistable gripper can automatically return to its initial state and release the target via a self-designed cable-driven mechanism. The ground-testing experiment demonstrates that the proposed soft gripper is capable to grasp, transfer, and release moving targets, and it thus possesses great potential to fulfill challenging operations in space missions.

[The Relationship between Speed of Platelet Recovery and Its R-squared and Efficacy after First Induction Chemotherapy in Acute Myeloid Leukemia].

OBJECTIVE: To calculate the cut-off values of speed of platelet recovery and its R-squared in patients with acute myeloid leukemia (AML) after initial induction chemotherapy, which were used to predict the complete remission (CR) of the first induction chemotherapy, and guide the clinic to choose the next appropriate chemotherapy regimen as soon as possible. METHODS: A total of 117 patients with newly diagnosed AML in the Second Hospital of Shanxi Medical University were included. Patients were diagnosed by morphology, immunology, cytogenetics, and molecular biology (MICM) classification, and the risk stratification was evaluated in combination with the clinical situations of the patients at the time of admission. The peripheral platelet counts after the first induction chemotherapy were detected and the linear regression equation was used to calculate the recovery speed of platelet counts in 5 consecutive blood cell analysis before discharge. According to the ROC curve, the cut-off value between the recovery speed and the R-squared was calculated, and the cut-off value was used to divide the patients into different groups. The differences between groups were compared by Pearson χ2 test to observe the remission effect of the first induction chemotherapy. RESULTS: ROC curve analysis showed that the cut-off value for predicting the platelet recovery speed and its R-squared of the first induction chemotherapy to achieve remission was 4.059 5×109/(L·d) and 72.7%, the sensitivity was 77% and 63.9%, the specificity was 62.5% and 67.9%, and the Youden index was 0.395 and 0.318, respectively. The patients were divided into different groups and compared according to the above cut-off values, and the results showed statistical differences (P<0.001, P=0.001). CONCLUSION: The cut-off value of platelet recovery speed and its R-squared after the first induction chemotherapy calculated by peripheral platelet count and ROC curve in AML patients can be used as an index to evaluate the remission. The faster the platelet recovery speed after chemotherapy is, the more likely patients achieve remission. The more stable the platelet recovery tendency is, the more likely patients achieve remission too.

Myoblast-derived exosomes promote the repair and regeneration of injured skeletal muscle in mice.

When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast-derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12-derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid-promoting factor peroxisome proliferator-activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen-1 and α-smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12-derived exosomes to SCs. Application of C2C12-derived exosomes to fibro-adipogenic progenitors resulted in an increase in peroxisome proliferator-activated receptor γ expression and adipogenesis capacity, whereas α-smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12-derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome-mediated regulation of the proliferation of SCs, differentiation of fibro-adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition.

Intelligent Evaluation of Stone Cell Content of Korla Fragrant Pears by Vis/NIR Reflection Spectroscopy.

Stone cells are a distinctive characteristic of pears and their formation negatively affects the quality of the fruit. To evaluate the stone cell content (SCC) of Korla fragrant pears, we developed a Vis/NIR spectroscopy system that allowed for the adjustment of the illuminating angle. The successive projective algorithm (SPA) and the Monte Carlo uninformative variable elimination (MCUVE) based on the sampling algorithm were used to select characteristic wavelengths. The particle swarm optimization (PSO) algorithm was used to optimize the combination of penalty factor C and kernel function parameter g. Support vector regression (SVR) was used to construct the evaluation model of the SCC. The SCC of the calibration set ranged from 0.240% to 0.657% and that of the validation set ranged from 0.315% to 0.652%. The SPA and MCUVE were used to optimize 57 and 83 characteristic wavelengths, respectively. The combinations of C and g were (6.2561, 0.2643) and (2.5133, 0.1128), respectively, when different characteristic wavelengths were used as inputs of SVR, indicating that the first combination had good generalization ability. The correlation coefficients of the SPA-SVR model after pre-processing the standardized normal variate (SNV) for both sets were 0.966 and 0.951, respectively. These results show that the SNV-SPA-SVR model satisfied the requirements of intelligent evaluation of SCC in Korla fragrant pears.

Association of Laryngopharyngeal Reflux Disease and Refractory Chronic Rhinosinusitis.

OBJECTIVE: The current study was conducted to explore the association between laryngopharyngeal reflux disease (LPRD) and refractory chronic rhinosinusitis (RCRS), and to reveal the potential role of LPRD in the development of RCRS. METHODS: A total of 104 patients diagnosed as chronic rhinosinusitis (CRS) and hospitalized, as well as 50 healthy participants were enrolled into this study. Among patients enrolled, 53 were RCRS and 51 were CRS. All participants were assessed with reflux symptom index (RSI) and reflux finding score (RFS). Patients with RSI >13 and/or RFS >7 were diagnosed as LPRD. In addition, pepsin in the nasal secretions from the middle meatus tract complex at fasting in the morning was analyzed using ELISA. Patients with pepsin concentration of >75 ng/ml was considered as positive, and confirmed as LPRD. RESULTS: There was no significant difference in age, sex, height, and weight among RCRS, CRS, and control groups. The positive rates of RSI and RFS scores were 39.6% in the RCRS and 52.9% in the CRS, respectively, which were significantly higher than that of the control group (14.0%, P < 0.05), respectively. Significantly higher positive rate of pepsin assay was also observed for RCRS(43.4%) and CRS(64.7%) when compared with the control group (18.0%, P < 0.05). The positive rate of pepsin assay was strongly associated with the positive rate of RSI or RFS (P < 0.001). CONCLUSION: The present findings have important implications that RSI and RFS score was highly associated with pepsin assay result in the patients with RCRS or CRS. We confirmed the importance of RSI and RFS scoring system as well as pepsin test, which may offer insight for clinical screening for LPRD among CRS patients.

Autosomal dominant lateral temporal epilepsy in a family exhibiting a rare heterozygous mutation and deletion in the leucine-rich glioma inactivated 1 gene.

Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. In a family with six ADLTE patients spanning four generations, our linkage and exome sequencing investigations revealed a rare frameshift heterozygous mutation in LGI1 (c.1494del(p.Phe498LeufsTer15)). Gene cloning methods were used to create plasmids with wild-type and mutant LGI1 alleles. Through transfection of HEK293 cells and primary neurons, they were utilized to assess the subcellular location of wild-type and mutant LGI1. Moreover, the plasmid-transfected primary neurons were analyzed for neuronal complexity and density of dendritic spines. According to our results. the mutation decreased LGI1 secretion in transfected HEK293 cells. In primary neurons, mutant LGI1 affected neuronal polarity and complexity. Our findings have broadened the phenotypic spectrum of LGI1 mutations and provided evidence regarding the pathogenicity of this mutation. In addition, we discovered new information about the role of LGI1 in the development of temporal lobe epilepsy, along with a possible link between neuronal polarity disorder and ADLTE.

Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report.

BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid ß-glucosidase activity [glucocerebrosidase (GCase)]. This study aimed to identify and characterise compound heterozygous mutations in GBA1 in a patient with type 1 GD. CASE SUMMARY: Here, we report a rare adult-onset type 1 GD in a 46-year-old female patient with clinical manifestations of giant spleen, thrombocytopenia, and bone pain, diagnosed by enzymatic and genetic testing. Enzymology and whole exome sequencing revealed heterozygous missense mutations in exon 10 c.1448T>C (p.L483P) and exon 7 c.928A>G (p.S310G) of GBA1. The latter was first reported in patients with GD. Structural modelling showed that p.S310G and p.L483P were distant from the GCase active site. The p.S310G mutation in domain 1 may decrease stability between the α2 and α3 helices of GBA1. The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminal ß-sheet. The patient was treated with imiglucerase replacement therapy, and her condition was stable. CONCLUSION: The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely affects GCase protein function. This is the first description of p.S310G being associated with mild type 1 GD in the context of a coinherited p.L483P mutation.