High Degree of Polymerization of Chitin Oligosaccharides Produced from Shrimp Shell Waste by Enrichment Microbiota Using Two-Stage Temperature-Controlled Technique of Inducing Enzyme Production and Metagenomic Analysis of Microbiota Succession.

The direct enzymatic conversion of untreated waste shrimp and crab shells has been a key problem that plagues the large-scale utilization of chitin biological resources. The microorganisms in soil samples were enriched in two stages with powdered chitin (CP) and shrimp shell powder (SSP) as substrates. The enrichment microbiota XHQ10 with SSP degradation ability was obtained. The activities of chitinase and lytic polysaccharide monooxygenase of XHQ10 were 1.46 and 54.62 U/mL. Metagenomic analysis showed that Chitinolyticbacter meiyuanensis, Chitiniphilus shinanonensis, and Chitinimonas koreensis, with excellent chitin degradation performance, were highly enriched in XHQ10. Chitin oligosaccharides (CHOSs) are produced by XHQ10 through enzyme induction and two-stage temperature control technology, which contains CHOSs with a degree of polymerization (DP) more significant than ten and has excellent antioxidant activity. This work is the first study on the direct enzymatic preparation of CHOSs from SSP using enrichment microbiota, which provides a new path for the large-scale utilization of chitin bioresources.

Robust Edge States of Quasi-1D Material Ta2NiSe7 and Applications in Saturable Absorbers.

The helical edge states (ESs) protected by underlying Z2 topology in two-dimensional topological insulators (TIs) arouse upsurges in saturable absorptions thanks to the strong photon-electron coupling in ESs. However, limited TIs demonstrate clear signatures of topological ESs at liquid nitrogen temperatures, hindering the applications of such exotic quantum states. Here, we demonstrate the existence of one-dimensional (1D) ESs at the step edge of the quasi-1D material Ta2NiSe7 at 78 K by scanning tunneling microscopy. Such ESs are rather robust against the irregularity of the edges, suggesting a possible topological origin. The exfoliated Ta2NiSe7 flakes were used as saturable absorbers (SAs) in an Er-doped fiber laser, hosting a mode-locked pulse with a modulation depth of up to 52.6% and a short pulse duration of 225 fs, far outstripping existing TI-based SAs. This work demonstrates the existence of robust 1D ESs and the superior SA performance of Ta2NiSe7.

Epitaxy of Antimonene Thin Films with Screw Dislocations for the Application of Saturable Absorbers.

The exotic optoelectronic properties of antimonene, including strain-induced tunable bandgaps, broad nonlinear refractive response, etc., have evoked profound upsurges for decades. As the screw dislocations break the crystal symmetry and modify interlayer coupling, it is highly desirable to investigate the optical prospects of antimonene with screw dislocations. Herein, controllable epitaxy of spiral ß-antimonene is achieved on Fe3GaTe2 substrates. By fine-tuning growth temperatures, the evolutions of spiral ß-antimonene with non-centrosymmetric stacking are investigated via scanning tunneling microscopy. The effects of interfacial strain and dislocation motion during screw-dislocation-driven growth are also studied. Additionally, a modulation depth of 40.8% and mode locking at 1558 nm with a pulse width of 290 fs are observed in Er-doped pulsed fiber lasers generated with spiral Sb-based saturable absorbers, revealing superior performance that far outstrips reported Sb-based saturable absorbers to date. Our work sheds light on the preparation of Sb films with screw dislocations and demonstrates a promising approach toward fabricating ultrafast optical devices.

Application of femtosecond mode-locked SnTe thin films and generation of bound-state solitons.

In the realm of ultrafast laser technology, the exploration of two-dimensional materials as saturable absorbers (SA) has garnered significant research interest. Our research investigates the characteristics of SnTe thin films, a topological crystalline insulator material, as a potential saturable absorber for ultrafast lasers. Using the molecular beam epitaxy (MBE) technique, we analyze the films' morphology and composition through atomic force microscopy (AFM) and successfully deposit SnTe epilayers on Au(111)/mica substrates. Through the utilization of SnTe-SA, an erbium-doped fiber laser is fabricated, demonstrating a pulse output with a width of 276 fs and a center wavelength of 1560 nm, highlighting the potential of SnTe films in manufacturing ultrafast optical devices. Additionally, tightly bound solitons with a soliton interval of 1.01 ps are observed, contributing to the exploration of soliton nonlinear dynamics.

Amino acids and their roles in tumor immunotherapy of breast cancer.

Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple-negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune-suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor-specific or oncogene-dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

A novel lytic polysaccharide monooxygenase from enrichment microbiota and its application for shrimp shell powder biodegradation.

Lytic polysaccharide monooxygenases (LPMO) are expected to change the current status of chitin resource utilization. This study reports that targeted enrichment of the microbiota was performed with chitin by the selective gradient culture technique, and a novel LPMO (M2822) was identified from the enrichment microbiota metagenome. First, soil samples were screened based on soil bacterial species and chitinase biodiversity. Then gradient enrichment culture with different chitin concentrations was carried out. The efficiency of chitin powder degradation was increased by 10.67 times through enrichment, and chitin degradation species Chitiniphilus and Chitinolyticbacter were enriched significantly. A novel LPMO (M2822) was found in the metagenome of the enriched microbiota. Phylogenetic analysis showed that M2822 had a unique phylogenetic position in auxiliary activity (AA) 10 family. The analysis of enzymatic hydrolysate showed that M2822 had chitin activity. When M2822 synergized with commercial chitinase to degrade chitin, the yield of N-acetyl glycosamine was 83.6% higher than chitinase alone. The optimum temperature and pH for M2822 activity were 35°C and 6.0. The synergistic action of M2822 and chitin-degrading enzymes secreted by Chitiniphilus sp. LZ32 could efficiently hydrolyze shrimp shell powder. After 12 h of enzymatic hydrolysis, chitin oligosaccharides (COS) yield reached 4,724 µg/mL. To our knowledge, this work is the first study to mine chitin activity LPMO in the metagenome of enriched microbiota. The obtained M2822 showed application prospects in the efficient production of COS.

New Insights into the Modification of the Non-Core Metabolic Pathway of Steroids in Mycolicibacterium and the Application of Fermentation Biotechnology in C-19 Steroid Production.

Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by Mycolicibacterium cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered mycolicibacterial strains has been effectively enhanced by sterol core metabolic modification. In recent years, research on the non-core metabolic pathway of steroids (NCMS) in mycolicibacterial strains has made significant progress. This review discusses the molecular mechanisms and metabolic modifications of NCMS for accelerating sterol uptake, regulating coenzyme I balance, promoting propionyl-CoA metabolism, reducing reactive oxygen species, and regulating energy metabolism. In addition, the recent applications of biotechnology in steroid intermediate production are summarized and compared, and the future development trend of NCMS research is discussed. This review provides powerful theoretical support for metabolic regulation in the biotransformation of phytosterols.

Mammalian Sterile 20-Like Kinase 1 Mediates Neuropathic Pain Associated with Its Effects on Regulating Mitophagy in Schwann Cells.

Myelin degradation initiated by Schwann cells (SCs) after nerve injury is connected to the induction and chronicity of neuropathic pain (NP). Mitophagy, a selective clearance of damaged mitochondria via autophagy, contributes to the maintenance of normal function in SCs. Mitochondrial function and mitophagy activity are highly modulated by mammalian ste20-like kinase1 (Mst1). However, whether Mst1 can regulate mitophagy in SCs to play a role in NP remains poorly understood. In the present study, Sprague-Dawley rats were subjected to chronic constriction injury (CCI) on the sciatic nerve to induce NP. Small interfering RNA of Mst1 was applied to the injured sciatic nerve to knockdown Mst1. Behavioral tests were performed to evaluate NP, and myelin degeneration was assessed by transmission electron microscope and immunofluorescence. Autophagy and mitophagy were detected in the injured sciatic nerve and cultured SCs (RSC96 cells) by Western blot. ROS level, mitochondria membrane potential, and apoptosis were assessed in vitro via flow cytometry and Western blot. Mst1 knockdown alleviated mechanical allodynia and thermal hyperalgesia in the CCI-induced NP model and rescued myelin degeneration of the injured nerve. Meanwhile, CCI-increased levels of Parkin and p62 were reversed by Mst1 knockdown. In vitro RSC96 cells were subjected to starvation to induce mitophagy. Protein levels of mitochondrial Parkin and mitochondrial p62 significantly increased after Mst1 knockdown, while those in the cytosol diminished indicate that the translocation of Parkin and p62 from the cytosol to the mitochondria was promoted by the knockdown of Mst1. In addition, Mst1 knockdown reduced ROS level and apoptosis activity, while enhancing mitochondria membrane potential in RSC96 cells. The study showed that Mst1 knockdown alleviated CCI-induced NP, associated with enhanced Parkin recruitment to mitochondria and subsequent mitophagy degradation, thus preserving mitochondrial function and myelin integrity.

UNC5B Overexpression Alleviates Peripheral Neuropathic Pain by Stimulating Netrin-1-Dependent Autophagic Flux in Schwann Cells.

Lesions or diseases of the somatosensory system can cause neuropathic pain (NP). Schwann cell (SC) autophagy plays an important role in NP. Uncoordinated gene 5 homolog B (UNC5B), the canonical dependent receptor of netrin-1, is known to be exclusively expressed in SCs and involved in NP; however, the underlying mechanisms were unclear. A rat model of sciatic nerve chronic constriction injury (CCI) was used to induce peripheral neuropathic pain. Adeno-associated virus (AAV) overexpressing UNC5B was applied to the injured nerve, and an autophagy inhibitor, 3-mechyladenine (3-MA), was intraperitoneally injected in some animals. Behavioral tests were performed to evaluate NP, the morphology of the injured nerves was analyzed, and autophagy-related proteins were detected. A rat SC line (RSC96) undergoing oxygen and glucose deprivation (OGD) was used to mimic an ischemic setting to examine the role of UNC5B in autophagy. Local UNC5B overexpression alleviated CCI-induced NP and rescued myelin degeneration. Meanwhile, UNC5B overexpression improved CCI-induced impairment of autophagic flux, while the autophagy inhibitor 3-MA reversed the analgesic effect of UNC5B. In cultured SCs, UNC5B helped recruit netrin-1 to the cell membrane. UNC5B overexpression promoted autophagic flux while inhibiting apoptosis, which was further augmented with exogenous netrin-1 and reversed by netrin-1 knockdown. The enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Unc51-like autophagy activating kinase 1 (ULK1) by UNC5B overexpression was also correlated with netrin-1. Our results suggest that UNC5B facilitates autophagic flux in SCs via phosphorylation of AMPK and ULK1, dependent on its ligand netrin-1, protecting myelin and partly preventing injury-induced NP.

Anti-GQ1b Antibody Syndrome with Visual Impairment: A Retrospective Case Series.

BACKGROUND: Anti-GQ1b antibody syndrome referred to a clinical spectrum characterized by acute onset of ataxia, ophthalmoplegia and areflexia, while visual deterioration was rarely reported in terms of ocular disorders. This study aimed to describe the clinical characteristics of anti-GQ1b antibody syndrome with visual impairment. METHODS: The database at the First Affiliated Hospital of Sun Yat-sen University was searched from 2014 to 2020. Patients with anti-GQ1b IgG were identified and divided into two groups according to the existence of optic neuropathy. Clinical and laboratory data of these subjects between the two groups were collected and analyzed. All patients were followed up by telephone to assess the outcome. RESULTS: A total of 12 patients with seropositive anti-GQ1b antibody were included, 75% of which got antecedent infection. Of these cases, 3 showed visual deterioration accompanied by abnormal orbital magnetic resonance imaging or visual evoked potentials, and the other 9 didn't show any evidence of vision impairment. Patients in the optic neuropathy group presented prominent visual impairments as initial symptoms and were more likely to suffer from facial weakness. There were 4 patients in normal visual acuity group complaining of blurred vision due to intraocular muscle paralysis, which was distinguished by subsequent examination. The combination of glucocorticoids and intravenous immunoglobulin was applied to treat patients with optic neuropathy. CONCLUSIONS: This study provides strong evidence that anti-GQ1b antibody syndrome can exhibit visual impairment, which helps further expand the clinical spectrum of anti-GQ1b antibody syndrome. More attention should be paid to the physical and supplementary ophthalmological examination to explore the pathogenesis and treatment of anti-GQ1b antibody syndrome.

The Physiological Significance of A-Waves in Early Diabetic Neuropathy: Assessment of Motor Nerve Fibers by Neurophysiological Techniques.

Objective: This study aimed to investigate how early A-waves could occur in type II diabetes, and what it implied functionally. Methods: We performed conduction velocity distribution (CVD) test in peroneal nerves of 37 type II diabetic patients with normal nerve conduction study (NCS) and 22 age-matched controls. The electrophysiological data and clinical information were analyzed. Results: A-waves were observed in 45.9% of diabetic patients and only in 1 person in healthy controls, all detected in the tibial nerves. The diabetic patients with A-waves showed faster conduction velocity in all quartiles in the motor peroneal nerves compared to the patients without A-waves, and their CVD histograms were shifted to the right side, consisting of a significantly larger percentage of fast conducting fibers. There was no significant difference in the CVD values of the upper extremity nerves among the patients with and without A-waves and the healthy controls. Conclusion: A-waves could occur in type II diabetes as early as when NCS showed normal, and represented as a sign of neuropathy as well as a sign of rescued motor nerve function.

Local uncoordinated gene 5H2 contributes to nerve injury-induced mechanical allodynia associated to its role in autophagy.

Lesions of the peripheral nerves can lead to lifelong neuropathic pain (NP). Autophagic deficiency in the Schwann cells (SCs) is an early event in the origin of NP chronification. Uncoordinated gene 5H2 (UNC5H2), one of the repulsive netrin receptors, mediated the effect of netrin-1 on autophagic activation and cell survival in endothelial cells. However, its role on autophagy regulation in peripheral nerves during NP process remains unidentified. Chronic constriction injury (CCI) of the left sciatic nerve was induced in Sprague-Dawley rats, and UNC5H2 small interfering RNA was transfected to the ipsilateral sciatic nerve immediately after injury. Mechanical allodynia was assessed. Sciatic UNC5H2 and netrin-1 protein levels were investigated. Autophagy in the ipsilateral sciatic nerves was evaluated by detecting punctate light chain 3(LC3) and autophagosomes, as well as the levels of LC3 II, p62 and phosphorylated UNC51-like kinase (ULK1). After CCI, UNC5H2 of the sciatic nerves was upregulated, exclusively expressed in SCs. Small interfering RNA transfection resulted in significant decrease of UNC5H2 and netrin-1 protein, leading to exaggeration of mechanical allodynia through 14 days after CCI. Autophagy was activated but autophagic influx was interfered within a week after CCI, shown by the elevated levels of both LC3II and p62, which was further deteriorated with UNC5H2 knockdown. In addition, the injury-induced augmentation of phosphorylated ULK1 was significantly diminished by UNC5H2 knockdown. Altogether, the results suggest that local UNC5H2 of the peripheral nerve plays a significant role in the process of injury-induced mechanical allodynia, probably associated to its contribution to autophagic regulation.

The rostral to caudal gradient of clinical and electrophysiological features in sporadic amyotrophic lateral sclerosis with bulbar-onset.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) with bulbar-onset (BO-ALS) tends to propagate to the adjacent anatomical regions symptomatically. However, the spreading pattern of clinical and electrophysiological features is not well documented. METHODS: This retrospective study enrolled consecutive patients with sporadic BO-ALS. The clinical progression and electrophysiological data by electromyography examination were retrospectively analysed based on information from the medical records. RESULTS: The study enrolled 57 patients: 43 presented with contiguous (37 of 57) or non-contiguous (6 of 57) progression clinically; and 14 patients did not present with symptomatic propagation to other spinal segments. Lower motor neuron dysfunction was more frequently involved in the bulbar and cervical segments and less in the thoracic and lumbosacral segments. As a result, a small proportion of patients had intact thoracic paraspinal or leg muscles or both by electromyography examination. Furthermore, the patients with diagnostic latency ≤6 months showed a significantly lower incidence of neurogenic changes in the lumbosacral spinal cord compared with those with diagnostic latency > 6 months. CONCLUSION: This current study demonstrated a relative rostral-caudal descending gradient of lower motor neuron dysfunction in patients with BO-ALS. These results suggest that follow-up EMG might be necessary for a proportion of patients.