Long-term follow-up of pallidal deep brain stimulation for craniocervical dystonia: is the globus pallidus internus the best target?

OBJECTIVE: Craniocervical dystonia (CCD) is a common type of segmental dystonia, which is a disabling disease that has been frequently misdiagnosed. Blepharospasm or cervical dystonia is the most usual symptom initially. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been widely used for treating CCD, its clinical outcome has been primarily evaluated in small-scale studies. This research examines the sustained clinical effectiveness of DBS of the GPi in individuals diagnosed with CCD. METHODS: The authors report 24 patients (14 women, 10 men) with refractory CCD who underwent DBS of the GPi between 2016 and 2023. The severity and disability of the dystonia were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS scores were collected preoperatively, 6 months postoperatively, and at the most recent follow-up visit. RESULTS: The mean age at onset was 52.0 ± 11.0 years (range 33-71 years) and the mean disease duration was 63.3 ± 73.3 months (range 7-360 months) (values for continuous variables are expressed as the mean ± SD). The mean follow-up period was 37.5 ± 23.5 months (range 6-84 months). The mean total BFMDRS motor scores at the 3 different time points were 13.3 ± 9.4 preoperatively, 5.0 ± 4.7 (55.3% improvement, p < 0.001) at 6 months, and 4.5 ± 3.6 (56.6% improvement, p < 0.001) at last follow-up. The outcomes were deemed poor in 6 individuals. CONCLUSIONS: Inferences drawn from the findings suggest that DBS of the GPi has long-lasting effectiveness and certain limitations in managing refractory CCD. The expected stability of the clinical outcome is not achieved. Patients with specific types of dystonia might consider targets other than GPi for a more precise therapy.

Functional response and predation rate of Cryptolaemus montrouzieri (Coleoptera: Coccinellidae) to Paracoccus marginatus (Hemiptera: Pseudococcidae) at different temperatures.

The ladybug, Cryptolaemus montrouzieri (Mulsant) (Coleoptera: Cocccinellidae)(Mulsant)(Coleoptera: Cocccinellidae), is a highly efficient predator in controlling mealybug populations and is considered an effective agent for controlling the papaya mealybugs (Paracoccus marginatus) (Williams & Granara de Willink) (Hemiptera: Pseudococcidae). Various criteria have been proposed for evaluating predator effectiveness, with the consumption rate of prey by individual predators, specifically the functional response, emerging as a common and crucial metric. This study evaluated the functional responses of third- and fourth-instar larvae, as well as male and female adults (<48 h old) of C. montrouzieri to adult females of P. marginatus at 3 different temperatures (22 °C, 28 °C, and 35 °C) with 70% ±â€…5% RH and a 12L:12D h photoperiod. Prey densities were 2, 4, 8, 16, 32, 45, or 60 papaya mealybugs per predator for all tests. The response to prey density by third- and fourth-instar larvae or both sexes of adult C. montrouzieri was a type II at all temperatures. The highest attack rate and lowest handling time were estimated at 28 °C in males and 35 °C in females, respectively. The highest daily prey consumption rate occurred at 35 °C in both the immature and adult stages of C. montrouzieri. These findings support the potential of C. montrouzieri in controlling the papaya mealybug, especially in tropical and subtropical regions, given its search efficiency at high temperatures tested in this study. However, additional field investigations are needed to ascertain the control efficacy of C. montrouzieri for this mealybug in biocontrol programs.

Development of a Bio-Hybrid Mosquito Stinger-Based Atomic Force Microscopy Probe.

Mosquitoes, notorious as the deadliest animals to humans due to their capacity to transmit diseases, pose a persistent challenge to public health. The primary prevention strategy currently in use involves chemical repellents, which often prove ineffective as mosquitoes rapidly develop resistance. Consequently, the invention of new preventive methods is crucial. Such development hinges on a thorough understanding of mosquito biting behaviors, necessitating an experimental setup that accurately replicates actual biting scenarios with controllable testing parameters and quantitative measurements. To bridge this gap, a bio-hybrid atomic force microscopy (AFM) probe was engineered, featuring a biological stinger - specifically, a mosquito labrum - as its tip. This bio-hybrid probe, compatible with standard AFM systems, enables a near-authentic simulation of mosquito penetration behaviors. This method marks a step forward in the quantitative study of biting mechanisms, potentially leading to the creation of effective barriers against vector-borne diseases (VBDs) and opening new avenues in the fight against mosquito-transmitted illnesses.

Mimicking the retinal neuron functions by a photoresponsive single transistor with a double gate.

To realize a low-cost neuromorphic visual system, employing an artificial neuron capable of mimicking the retinal neuron functions is essential. A photoresponsive single transistor neuron composed of a vertical silicon nanowire is proposed. Similar to retinal neurons, various photoresponsive characteristics of the single transistor neuron can be modulated by light intensity as well as wavelength and have a high responsivity to green light like the human eye. The device is designed with a cylindrical surrounding double-gate structure, enclosed by an independently controlled outer gate and inner gate. The outer gate has the function of selectively inhibiting neuron activity, which can mimic lateral inhibition of amacrine cells to ganglion cells, and the inner gate can be utilized for the adjustment of the firing threshold voltage, which can be used to mimic the regulation of photoresponsivity by horizontal cells for adaptive visual perception. Furthermore, a myelination function that controls the speed of information transmission is obtained according to the inherent asymmetric source/drain structure of a vertical silicon nanowire. This work can enable photoresponsive neuronal function using only a single transistor, providing a promising hardware implementation for building miniaturized neuromorphic vision systems at low cost.

Regulatory Mechanism through Which Old Soybean Leaves Respond to Mn Toxicity Stress.

Manganese (Mn) is a heavy metal that can cause excessive Mn poisoning in plants, disrupting microstructural homeostasis and impairing growth and development. However, the specific response mechanisms of leaves to Mn poisoning have not been fully elucidated. This study revealed that Mn poisoning of soybean plants resulted in yellowing of old leaves. Physiological assessments of these old leaves revealed significant increases in the antioxidant enzymes activities (peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)) and elevated levels of malondialdehyde (MDA), proline, indoleacetic acid (IAA), and salicylic acid (SA), under 100 µM Mn toxicity. Conversely, the levels of abscisic acid (ABA), gibberellin 3 (GA3), and jasmonic acid (JA) significantly decreased. The Mn content in the affected leaves significantly increased, while the levels of Ca, Na, K, and Cu decreased. Transcriptome analysis revealed 2258 differentially expressed genes in the Mn-stressed leaves, 744 of which were upregulated and 1514 were downregulated; these genes included genes associated with ion transporters, hormone synthesis, and various enzymes. Quantitative RT-PCR (qRT-PCR) verification of fifteen genes confirmed altered gene expression in the Mn-stressed leaves. These findings suggest a complex gene regulatory mechanism under Mn toxicity and stress, providing a foundation for further exploration of Mn tolerance-related gene regulatory mechanisms in soybean leaves. Using the methods described above, this study will investigate the molecular mechanism of old soybean leaves' response to Mn poisoning, identify key genes that play regulatory roles in Mn toxicity stress, and lay the groundwork for cultivating high-quality soybean varieties with Mn toxicity tolerance traits.

A study on the association between prefrontal functional connectivity and non-suicidal self-injury in adolescents with depression.

Objective: Among adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression. Methods: A total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants' brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores. Result: Compared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = -0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = -0.438, p = 0.012, respectively). Conclusion: Adolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior.

Increased water content in multifidus muscles of young adults with chronic nonspecific low back pain detected by dual-energy CT and MRI.

OBJECTIVES: To demonstrate the feasibility of better diagnosing young adults with chronic nonspecific low back pain (CNLBP) by measuring water content in paraspinal muscles using water-muscle decomposition technique in dual-energy CT (DECT) and T2-mapping in MRI. METHODS: This prospective cross-sectional study included 110 young individuals (56 with CNLBP at age of 25.7 ± 2.0 years and 54 of asymptomatic at age of 25.1 ± 1.9 years) who underwent both MRI and DECT on the spine. T2 values on T2 mapping in MRI and water density (WD) value on water(muscle) images in DECT were generated at the L1-L4 levels for erector spinae muscle and L2-L5 for multifidus muscle. Pain duration time, Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) were recorded for CNLBP patients. Difference of T2 value and WD between the two patient groups, and correlations between T2 value and WD, and T2 value and WD with clinical indicators were analyzed. RESULTS: Compared with asymptomatic participants, the mean WD of multifidus muscle at L4-L5 and mean T2 values of multifidus muscle at L5 were significantly higher in CNLBP patients (all P < 0.05). T2 values had moderate to strong positive correlations (r = 0.34-0.60, all P < 0.05) with DECT WD in CNLBP patients and healthy volunteers. There was a weak correlation between VAS and WD in L5-level multifidus muscle (r = 0.29, P < 0.05). CONCLUSIONS: The T2 values in MRI and WD in DECT are higher in multifidus muscles of lower vertebra levels for young CNLBP patients, and there exists positive correlation between WD and T2 values, providing useful information for diagnosing CNLBP.

Enhancement of Strength-Ductility Synergy of Al-Li Cast Alloy via New Forming Processes and Sc Addition.

In this study, concurrent enhancements in both strength and ductility of the Al-2Li-2Cu-0.5Mg-0.2Zr cast alloy (hereafter referred to as Al-Li) were achieved through an optimized forming process comprising ultrasonic treatment followed by squeeze casting, coupled with the incorporation of Sc. Initially, the variations in the microstructure and mechanical properties of the Sc-free Al-Li cast alloy (i.e., alloy A) during various forming processes were investigated. The results revealed that the grain size in the UT+SC (ultrasonic treatment + squeeze casting) alloy was reduced by 76.3% and 57.7%, respectively, compared to those of the GC (gravity casting) or SC alloys. Additionally, significant improvements were observed in its compositional segregation and porosity reduction. After UT+SC, the ultimate tensile strength (UTS), yield strength (YS), and elongation reached 235 MPa, 135 MPa, and 15%, respectively, which were 113.6%, 28.6%, and 1150% higher than those of the GC alloy. Subsequently, the Al-Li cast alloy containing 0.2 wt.% Sc (referred to as alloy B) exhibited even finer grains under the UT+SC process, resulting in simultaneous enhancements in its UTS, YS, and elongation. Interestingly, the product of ultimate tensile strength and elongation (i.e., UTS × EL) for both alloys reached 36 GPa•% and 42 GPa•%, respectively, which is much higher than that of other Al-Li cast alloys reported in the available literature.

Strigolactones alleviate AlCl3 stress by vacuolar compartmentalization and cell wall blocking in apple.

Poor management and excess fertilization of apple (Malus domestica Borkh.) orchards are causing increasingly serious soil acidification, resulting in Al toxicity and direct poisoning of roots. Strigolactones (SLs) are reported to be involved in plant responses to abiotic stress, but their role and mechanism under AlCl3 stress remain unknown. Here, we found that applying 1 µm GR24 (an SL analoge) significantly alleviated AlCl3 stress of M26 apple rootstock, mainly by blocking the movement of Al through cell wall and by vacuolar compartmentalization of Al. RNA-seq analysis identified the core transcription factor gene MdWRKY53, and overexpressing MdWRKY53 enhanced AlCl3 tolerance in transgenic apple plants through the same mechanism as GR24. Subsequently, we identified MdPMEI45 (encoding pectin methylesterase inhibitor) and MdALS3 (encoding an Al transporter) as downstream target genes of MdWRKY53 using chromatin immunoprecipitation followed by sequencing (ChIP-seq). GR24 enhanced the interaction between MdWRKY53 and the transcription factor MdTCP15, further increasing the binding of MdWRKY53 to the MdPMEI45 promoter and inducing MdPMEI45 expression to prevent Al from crossing cell wall. MdWRKY53 also bound to the promoter of MdALS3 and enhanced its transcription to compartmentalize Al in vacuoles under AlCl3 stress. We therefore identified two modules involved in alleviating AlCl3 stress in woody plant apple: the SL-WRKY+TCP-PMEI module required for excluding external Al by blocking the entry of Al3+ into cells and the SL-WRKY-ALS module allowing internal detoxification of Al through vacuolar compartmentalization. These findings lay a foundation for the practical application of SLs in agriculture.

Trehalose enhanced cold atmospheric plasma-mediated cancer treatment.

Cold atmospheric plasma (CAP) is a unique form of physical plasma that has shown great potential for cancer therapy. CAP uses ionized gas to induce lethal oxidative stress on cancer cells; however, the efficacy of CAP therapy continues to be improved. Here, we report an injectable hydrogel-mediated approach to enhance the anti-tumor efficacy of CAP by regulating the phosphorylation of eIF2α. We discovered that reactive oxygen and nitrogen species (ROS/RNS), two main anti-tumor components in CAP, can lead to lethal oxidative stress on tumor cells. Elevated oxidative stress subsequently induces eIF2α phosphorylation, a pathognomonic marker of immunogenic cell death (ICD). Trehalose, a natural disaccharide sugar, can further enhance CAP-induced ICD by elevating the phosphorylation of eIF2α. Moreover, injectable hydrogel-mediated delivery of CAP/trehalose treatment promoted dendritic cell (DC) maturation, initiating tumor-specific T-cell mediated anti-tumor immune responses. The combination therapy also supported the polarization of tumor-associated macrophages to an M1-like phenotype, reversing the immunosuppressive tumor microenvironment and promoting tumor antigen presentation to T cells. In combination with immune checkpoint inhibitors (i.e., anti-programmed cell death protein 1 antibody, aPD1), CAP/trehalose therapy further inhibited tumor growth. Importantly, our findings also indicated that this hydrogel-mediated local combination therapy engaged the host systemic innate and adaptive immune systems to impair the growth of distant tumors.

Viscoelastic hydrogels regulate adipose-derived mesenchymal stem cells for nucleus pulposus regeneration.

Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation. However, the impact of tissue-specific viscoelasticity on the activities of adipose-derived stem cells (ASC) remains largely unexplored. Here, we investigated the role of matrix viscoelasticity in regulating ASC differentiation for IVD regeneration. Viscoelastic alginate hydrogels with stress relaxation time scales ranging from 100 s to 1000s were developed and used to culture human ASCs for 21 days. Our results demonstrated that the fast-relaxing hydrogel significantly enhanced ASCs long-term cell survival and NP-like extracellular matrix secretion of aggrecan and type-II collagen. Moreover, gene expression analysis revealed a substantial upregulation of the mechanosensitive ion channel marker TRPV4 and NP-specific markers such as SOX9, HIF-1α, KRT18, CDH2 and CD24 in ASCs cultured within the fast-relaxing hydrogel, compared to slower-relaxing hydrogels. These findings highlight the critical role of matrix viscoelasticity in regulating ASC behavior and suggest that viscoelasticity is a key parameter for novel biomaterials design to improve the efficacy of stem cell therapy for IVD regeneration. STATEMENT OF SIGNIFICANCE: Systematically characterized the influence of tissue-mimetic viscoelasticity on ASC. NP-mimetic hydrogels with tunable viscoelasticity and tissue-matched stiffness. Long-term survival and metabolic activity of ASCs are substantially improved in the fast-relaxing hydrogel. The fast-relaxing hydrogel allows higher rate of cell protrusions formation and matrix remodeling. ASC differentiation towards an NP-like cell phenotype is promoted in the fast-relaxing hydrogel, with more CD24 positive expression indicating NP committed cell fate. The expression of TRPV4, a molecular sensor of matrix viscoelasticity, is significantly enhanced in the fast-relaxing hydrogel, indicating ASC sensing matrix viscoelasticity during cell development. The NP-specific ECM secretion of ASC is considerably influenced by matrix viscoelasticity, where the deposition of aggrecan and type-II collagen are significantly enhanced in the fast-relaxing hydrogel.

Solibacillus ferritrahens sp. nov., a novel siderophore-producing bacterium isolated from Wumeng Mountain National Nature Reserve in Yunnan Province.

A gram-stain-positive, aerobic, rod-shaped bacterial strain capable of producing siderophores, named YIM B08730T, was isolated from a soil sample collected from Wumeng Mountain National Nature Reserve, Zhaotong City, Yunnan Province. Growth occurred at 10-45 °C (optimum, 35-40 â„ƒ), pH 7.0-9.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0-1 %, w/v). A comparative analysis of the 16S rRNA gene sequence (1558 bp) of strain YIM B08730T showed the highest similarity to Solibacillus isronensis JCM 13838T (96.2 %), followed by Solibacillus silvestris DSM 12223T (96.0 %) and Solibacillus kalamii ISSFR-015T (95.4 %). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unidentified lipid. The main respiratory quinone of strain YIM B08730T was menaquinone 7 (MK-7). The major fatty acids were iso-C15:0 and C16:1ω7c alcohol. The digital DNA-DNA hybridization and average nucleotide identity values between strain YIM B08730T and the reference strain S. isronensis JCM 13838T were 24.8 % and 81.2 %, respectively. The G + C content of the genomic DNA was 37.1 mol%. The genome of the novel strain contained genes associated with the production of siderophores, and it also revealed other functional gene clusters involved in plant growth promotion and soil bioremediation. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B08730T is considered to be a novel species of the genus Solibacillus, for which the name Solibacillus ferritrahens sp. nov. is proposed. The type strain is YIM B08730T (= NBRC 116268T = CGMCC 1.60169T).

Thermal acclimation uncovers a simple genetic basis of adaptation to high temperature in a cosmopolitan pest.

Understanding a population's fitness heterogeneity and genetic basis of thermal adaptation is essential for predicting the responses to global warming. We examined the thermotolerance and genetic adaptation of Plutella xylostella to exposure to hot temperatures. The population fitness parameters of the hot-acclimated DBM strains varied in the thermal environments. Using genome scanning and transcription profiling, we find a number of genes potentially involved in thermal adaptation of DBM. Editing two ABCG transporter genes, PxWhite and PxABCG, confirmed their role in altering cuticle permeability and influencing thermal responses. Our results demonstrate that SNP mutations in genes and changes in gene expression can allow DBM to rapidly adapt to thermal environment. ABCG transporter genes play an important role in thermal adaptation of DBM. This work improves our understanding of genetic adaptation mechanisms of insects to thermal stress and our capacity to predict the effects of rising global temperatures on ectotherms.

Investigating the ERG a-wave and Retinal Diseases with Rod Equivalent Circuit Model Based on the APD.

Most empirically supported mathematical models of rod cells lack theoretical support from actual physical devices. Therefore, this paper proposes an equivalent circuit model for the rod is proposed based on the photoconductive properties of the avalanche photodetector (APD) and combined with the electrical properties of the rod. The model employs the photodetector to simulate the source of the photocurrent in outer segments of rod cells and takes into account the electrical properties of the inner and outer segments, the nucleus, and the synaptic terminals. It successfully simulates the trans-retinal voltage generated by the intracellular and extracellular flow of photocurrent in the outer segment of dark-adapted rods. Moreover, the typical waveform characteristics of two retinal diseases, the enhanced short wavelength sensitivity (SWS) cone syndrome and retinitis pigmentosa (RP), are investigated on the basis of electroretinogram (ERG) a-wave. This will further elucidate the function of the visual system and the ERG a-wave characteristics of the related diseases. Comparison with published experimental results validates the reliability of the model presented. Our study provides new ideas and strategies for the diagnosis of retinal diseases and provides some theoretical support for the application of photodetectors in the fabrication of artificial retinal devices.

Fibrin clot fracture under cyclic fatigue and variable rate loading.

Fibrin clot is a vital class of fibrous materials, governing the mechanical response of blood clots. Fracture behavior of fibrin clots under complex physiological load is relevant for hemostasis and thrombosis. But how they fracture under cyclic and variable rate loading has not been reported. Here we conduct cyclic fatigue and monotonic variable rate loading tests on fibrin clots to characterize their fracture properties in terms of fatigue threshold and rate-dependent fracture toughness. We demonstrate that the fracture behavior of fibrin clots is sensitive to the amplitude of cyclic load and the loading rate. The cyclic fatigue tests show the fatigue threshold of fibrin clots at 1.66 J/m2, compared to the overall fracture toughness 15.8 J/m2. Furthermore, we rationalize the fatigue threshold using a semi-empirical model parameterized by 3D morphometric quantification to account for the hierarchical molecular structure of fibrin fibers. The variable loading tests reveal rate dependence of the overall fracture toughness of fibrin clots. Our analysis with a viscoelastic fracture model suggests the viscoelastic origin of the rate-dependent fracture toughness. The toughening mechanism of fibrin clots is further compared with biological tissues and hydrogels. This study advances the understanding and modeling of fatigue and fracture of blood clots and would motivate further investigation on the mechanics of fibrous materials. STATEMENT OF SIGNIFICANCE: Fibrin clot is a soft fibrous gel, exhibiting nonlinear mechanical responses under complex physiological loads. It is the main load-bearing constituent of blood clots where red blood cells, platelets and other cells are trapped. How the fibrin clot fractures under complex mechanical loads is critical for hemostasis and thrombosis. We study the fracture behavior of fibrin clots under cyclic fatigue and monotonic variable rate loads. We characterize the fatigue-threshold and viscous energy dissipation of fibrin clots. We compare the toughness enhancement of fibrin clots with hydrogels. The findings offer new insights into the fatigue and fracture of blood clots and fibrous materials, which could improve design guidelines for bioengineered materials.

Asymmetric α-C(sp3)-H allylic alkylation of primary alkylamines by synergistic Ir/ketone catalysis.

Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C-H bonds are unreactive towards electrophiles due to their extremely low acidity (pKa ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary alkyl amines by increasing the acidity of the α-amino C-H bonds by up to 1044 times. This makes the α-amino C-H bonds acidic enough to be deprotonated under mild conditions. By combining DFO with an iridium catalyst, direct asymmetric α-C-H alkylation of NH2-unprotected primary alkyl amines with allylic carbonates has been achieved. This reaction produces a wide range of chiral homoallylic amines with high enantiopurities. The approach has successfully switched the reactivity between primary alkyl amines and allylic carbonates from intrinsic allylic amination to the α-C-H alkylation, enabling the construction of pharmaceutically significant chiral homoallylic amines from readily available primary alkyl amines in a single step.

Injectable hydrogel induces regeneration of naturally degenerate human intervertebral discs in a loaded organ culture model.

Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc (IVD). This study investigates the ability of an injectable hydrogel (NPgel), to inhibit catabolic protein expression and promote matrix expression in human nucleus pulposus (NP) cells within a tissue explant culture model isolated from degenerate discs. Furthermore, the injection capacity of NPgel into naturally degenerate whole human discs, effects on mechanical function, and resistance to extrusion during loading were investigated. Finally, the induction of potential regenerative effects in a physiologically loaded human organ culture system was investigated following injection of NPgel with or without bone marrow progenitor cells. Injection of NPgel into naturally degenerate human IVDs increased disc height and Young's modulus, and was retained during extrusion testing. Injection into cadaveric discs followed by culture under physiological loading increased MRI signal intensity, restored natural biomechanical properties and showed evidence of increased anabolism and decreased catabolism with tissue integration observed. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. STATEMENT OF SIGNIFICANCE: Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc. This study investigated the potential regenerative properties of an injectable hydrogel system (NPgel) within human tissue samples. To mimic the human in vivo conditions and the unique IVD niche, a dynamically loaded intact human disc culture system was utilised. NPgel improved the biomechanical properties, increased MRI intensity and decreased degree of degeneration. Furthermore, NPgel induced matrix production and decreased catabolic factors by the native cells of the disc. This manuscript provides evidence for the potential use of NPgel as a regenerative biomaterial for intervertebral disc degeneration.

Treatment of non-small cell lung cancer with Yiqi Buxue prescriptions combined with adjuvant chemotherapy on the cancer therapy-related cardiovascular toxicity: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment and prognosis of patients with non-small cell lung cancer (NSCLC) was affected by the occurrence of cancer therapy-related cardiovascular toxicity (CTR-CVT). Yiqi Buxue prescriptions were a class of traditional single or compounded formulations that have become a consensus for NSCLC. There was no clear information and or summary available for Yiqi Buxue prescriptions combined with adjuvant chemotherapy for NSCLC in reducing CTR-CVT. AIM OF THE STUDY: To systematically evaluate the Yiqi Buxue prescriptions combined with adjuvant chemotherapy in reducing CTR-CVT for patients with NSCLC. MATERIALS AND METHODS: Search strategies were developed to identify relevant randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure (CNKI), SinoMed and WanFang Data from database inception date to October 2022. The methodological quality of evidence was assessed using the Cochrane risk of bias (ROBs) assessment tool, and the meta-analysis was analyzed using RevMan 5.3. RESULTS: A total of 9 studies were included. Compared with the adjuvant chemotherapy group, Yiqi Buxue prescriptions combined with adjuvant chemotherapy group showed no statistically significant in reducing CTR-CVT (RR 0.67, 95%CI 0.11 to 3.93, P = 0.65) and in CD4+/CD8+(MR 0.32, 95%CI -0.13 to 0.77, P = 0.16). However, it significantly improved the objective response rate (ORR) (RR 1.57, 95%CI 1.32 to 1.87, P < 0.00001), disease control rate (DCR) (RR 1.25, 95%CI 1.15 to 1.35, P < 0.00001), Karnofsky performance status (KPS) improvement rate (RR 1.34, 95%CI 1.16 to 1.55, P < 0.0001), CD3+ (MR 4.17, 95%CI 3.68 to 4.66, P < 0.00001), CD4+ (MR 4.87, 95%CI 4.28 to 5.46, P < 0.00001), and CD8+ (MR 3.12, 95%CI 2.57 to 3.67, P < 0.00001). CONCLUSIONS: The current RCTs are hampered by small sample sizes and poor methodological quality. More rigorously designed and large sample RCTs with primary outcome of CTR-CVT are needed to investigate the effectiveness of Yiqi Buxue prescriptions combined with adjuvant chemotherapy in reducing CTR-CVT for patients with NSCLC.

Tough gel adhesive is an effective method for meniscal repair in a bovine cadaveric study.

PURPOSE: To test tough gel adhesives to repair meniscus tears under relevant loading conditions and determine if they have adequate biomechanical properties to repair meniscus tears in a bovine cadaveric study. METHODS: Cyclic compression tests on 24 dissected bovine knees were performed. The tough gel adhesive was used either as an adhesive patch or as a coating bonded onto commercially available surgical sutures. Forty-eight menisci were tested in this study; 24 complete radial tears and 24 bucket-handle tears. After preconditioning, the specimens underwent 100 cycles of compression, (800 N/0.5 Hz) on an Instron© machine and the size of the gaps measured. One third of the menisci were repaired with pristine sutures, one third with adhesive patches, and one third with sutures coated in adhesive gel. The size of the gaps was compared after 100 and 500 cycles of compression. RESULTS: The mean gap measured at the tear site without treatment was 6.46 mm (± 1.41 mm) for radial tears and 1.92 mm (± 0.65 mm) for bucket-handle tears. After treatment and 500 cycles of compression, the mean gap was 1.63 mm (± 1.41 mm) for pristine sutures, 1.50 mm (± 1.16 mm) for adhesive sutures and 2.06 mm (± 1.53 mm) for adhesive gel patches. There was no significant difference between treatments regardless of the type of tear. Also, the gaps for radial tears increased significantly with the number of compression cycles applied (p > 0.001). CONCLUSION: From a biomechanical standpoint, the tough adhesive gel patch is as effective as suturing. In addition, it would allow the repair of non-suturable tears and thus broaden the indications for meniscus repair. LEVEL OF EVIDENCE: Controlled laboratory study.

Efficient and systematic parameter extraction based on rate equations by DFB equivalent circuit model.

The conventional direct parameter extraction method generally suffers from cumbersome due to redundant experiments. An efficient and systematical parameter extracting solution is proposed based on an equivalent circuit model of distributed feedback (DFB) lasers. The successfully built circuit model includes the necessary intrinsic parameters in the rate equations and the extrinsic parameters to provide a better approximation of the actual laser. This method is experimentally verified through a DFB laser chip measurement of electronic and optical performance under the same conditions. Finally, the nine intrinsic parameters in the rate equations and five extrinsic parameters in the model are efficiently extracted using this technique from a set of experimental characteristics of a DFB laser chip. Modeled and measured results for the laser output characteristics exhibit good agreement when the extracted parameters are used. The method is versatile for other semiconductor lasers that can be modeled using rate equations. Comparison with simulation results of published laser models further validates the reliability of the presented model and extraction method.