The Evolution of Curve Patterns in Adolescent Idiopathic Scoliosis during Chêneau Brace Treatment.

STUDY DESIGN/SETTING: This retrospective study analyzed bracing outcomes in AIS patients, focusing on curve pattern changes and brace efficacy. OBJECTIVE: To analyze the effectiveness of the Chêneau brace across different curve patterns and to evaluate the tendencies in curve evolution during treatment. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis (AIS) presents diverse curve patterns, each responding differently to bracing. Understanding these variations is crucial for optimizing treatment strategies. METHODS: The study included 177 AIS patients treated with Chêneau orthoses, categorized based on curve patterns as per the main curve and modified Lenke (mLenke) classifications. We compared patients according to curve patterns and assessed changes in curve magnitude and pattern before and after treatment. RESULTS: Over an average follow-up of 28.1±10.7 months, the primary curve magnitude decreased from 28.8±6.6° to 25.9±10.5°. Significant reductions were observed in mLenke V and VI patients (P<0.05). Patients with main lumbar curves showed better initial in-brace correction and curve control compared with those with main thoracic curves (P<0.05). In single-curve patterns, binary logistic regression indicated that mLenke V patients demonstrated higher rates of curve control compared with mLenke I patients (P<0.05). No significant differences were found in double-curve patterns between mLenke III and VI (P>0.05). At the final follow-up, thoracolumbar/lumbar curves improved significantly in mLenke III and VI patients (P<0.05), while thoracic curves did not (P>0.05). Furthermore, at the last follow-up, the proportions of mLenke I, II, and IV increased, while mLenke III, V, and VI decreased. CONCLUSIONS: Bracing outcomes were more favorable in patients with main lumbar curves than those with main thoracic curves. However, no significant differences were found in patients with double-curve patterns. Thoracic curves exhibited a higher progression risk compared with thoracolumbar/lumbar curves within the same curve pattern. During bracing, a tendency for primary curves to shift proximally was noted.

Dwell time for optical fabrication using the modified discrete convolution matrix method.

More accurate dwell time calculation methods are necessary to achieve superior error convergence in producing optically critical components. Although the discrete convolution matrix method finds widespread application, it still has approximate errors in the non-uniform discrete form of tool paths. To address this issue, this paper introduced a modified matrix elements method and presented the general Voronoi polygon area weight calculation forms under different tool path discretization forms. The mechanism is explained through analysis and the validity is verified by numerical simulation. The modified method significantly improved uniformity distribution and accuracy in computation of surface residuals. This improvement holds promise as a guiding principle for the fabrication of ultra-precision optical components.

Bismuth Chelate-Mediated Digital Subtraction Angiography.

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200 g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5 mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.

High precision polishing of aluminum alloy mirrors through a combination of magnetorheological finishing and chemical mechanical polishing.

After the aluminum alloy mirror machined by single point diamond turning (SPDT), the residual tool marks and surface accuracy of the aluminum alloy mirror cannot meet the requirements of visible or ultraviolet light system. In this study, a processing method combining magnetorheological finishing (MRF) and chemical mechanical polishing (CMP) is proposed to realize the polishing of aluminum alloy mirrors with high efficiency, high precision and high-quality. Firstly, the properties and composition of passivation layer after MRF were analyzed and the polishing performance of acidic, neutral and alkaline alumina polishing fluid on passivation layer were investigated based on the computer numerical control (CNC) polishing equipment. Based on the experimental results, a new acidic nano-silica polishing fluid which is suitable for the efficient and high-quality removal of passivation layers on aluminum alloy surfaces was developed. Finally, a combined approach of MRF-CMP was used to the directly polishing of a rapidly solidified aluminum mirror (RSA-6061) with a diameter of 100 mm after SPDT. With two iterative of MRF-CMP polishing in 220 minutes, the surface accuracy of the aluminum alloy mirror was improved from 0.1λ (λ=632.8 nm) to 0.024λ, and the surface roughness (Ra) decreased from 3.6 nm to 1.38 nm. The experiment results manifest that high precision, and high-quality aluminum alloy mirror can be achieved by MRF-CMP method with the new developed acid nano-silica polishing fluid and suitable MR polishing fluid. The research results will provide a new strategy for ultra-precision direct polishing of aluminum alloy mirrors and will also give the important technical support for the extensive use of aluminum alloy mirror in visible light and ultraviolet optical systems.

Surgical treatment for congenital vertebral anomalies with bilateral bifid intrathoracic rib in association: A series of five cases.

Background: Congenital scoliosis is often associated with costal deformities, of which a bilateral bifid intrathoracic rib is very rare. The aim of this study was to retrospectively summarize the clinical manifestations, imaging characteristics, treatment strategies, and postoperative outcomes of five patients with bilateral bifid intrathoracic rib. Methods: We retrospectively reviewed the imaging findings and medical records of five pediatric patients (two girls, three boys) with bilateral bifid intrathoracic rib who were surgically treated for congenital kyphoscoliosis (mean age = 8 years). The clinical manifestations, imaging characteristics, treatment strategies, and postoperative outcome were summarized. Results: Four of five patients showed abnormalities from birth. All five patients presented with kyphoscoliosis and a fused vertebral body or lamina. The bilateral bifid intrathoracic rib was located at T2-3 in three patients, T7 in one patient, and T10 in one patient. Various congenital spinal deformities and multiple system malformations were present in all five patients. Three patients had preoperative neurological deficits. For corrective surgery, one patient received a traditional growing rod implantation, one patient underwent resection of a bony septum, and three patients underwent spinal osteotomy. One patient suffered complete paralysis of the lower limbs after surgery. Conclusion: Bilateral bifid intrathoracic rib is a rare anomaly that typically occurs in patients with serious kyphoscoliosis. Bilateral bifid intrathoracic rib patients show similar clinical and radiological characteristics and are likely to exhibit neurological deficits before or following corrective surgery. Spinal surgeons should be aware of the high risk of permanent neurological complications related to surgery in these patients. Level of evidence: level IV.

Associated injuries and complications in pediatric pelvic fractures requiring hospitalization: A series of 315 cases.

Purpose: Pediatric pelvic fractures are uncommon. This study aimed to investigate the clinical characteristics of pediatric pelvic fractures requiring hospitalization and analyze their correlation with associated injuries and complications. Methods: Data from 315 pediatric pelvic fracture patients admitted to our hospital from January 2006 to December 2021 were retrospectively analyzed. Sex, age, modified Torode-Zieg classification, abbreviated injury scale score, injury severity score, mortality, and concomitant injuries were analyzed. Results: Of the 285 (90.5%) cases of combined injuries, most injuries occurred in the abdomen (64.8%) and lower extremities (47.6%), followed by the chest (45.4%) and head (34.6%). A total of 78 patients (24.8%) were transferred to the intensive care unit. In total, 94 patients (29.8%) had complications during hospitalization. There were differences based on injury mechanism (p = 0.001), with the highest complication rate in the fall injury group (32 cases (46.4%)). Approximately 51.4% of patients received surgical treatment for problems that were not related to pelvic fractures. Among these, 30.2% necessitated surgical intervention on the lower limbs. Abdominal surgery was necessary in 19.0% of patients. Conclusions: Children who have pelvic fractures frequently require hospitalization due to the presence of severe injuries in other areas of their bodies. IIIB pelvic fractures frequently occur in conjunction with more severe abdominal injuries; therefore, the prompt management of cavity and organ injuries is of particular importance. Blood transfusion and injury severity score were associated risk factors for intensive care unit admission.

Screening structure and predicting toxicity of pesticide adjuvants using molecular dynamics simulation and machine learning for minimizing environmental impacts.

Surfactants as synergistic agents are necessary to improve the stability and utilization of pesticides, while their use is often accompanied by unexpected release into the environment. However, there are no efficient strategies available for screening low-toxicity surfactants, and traditional toxicity studies rely on extensive experimentation which are not predictive. Herein, a commonly used agricultural adjuvant Triton X (TX) series was selected to study the function of amphipathic structure to their toxicity in zebrafish. Molecular dynamics (MD) simulations, transcriptomics, metabolomics and machine learning (ML) were used to study the toxic effects and predict the toxicity of various TX. The results showed that TX with a relatively short hydrophilic chain was highly toxic to zebrafish with LC50 of 1.526 mg/L. However, TX with a longer hydrophilic chain was more likely to damage the heart, liver and gonads of zebrafish through the arachidonic acid metabolic network, suggesting that the effect of surfactants on membrane permeability is the key to determine toxic results. Moreover, biomarkers were screened through machine learning, and other hydrophilic chain lengths were predicted to affect zebrafish heart health potentially. Our study provides an advanced adjuvants screening method to improve the bioavailability of pesticides while reducing environmental impacts.

NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

Staging of Liver Fibrosis Based on Energy Valley Optimization Multiple Stacking (EVO-MS) Model.

Currently, staging the degree of liver fibrosis predominantly relies on liver biopsy, a method fraught with potential risks, such as bleeding and infection. With the rapid development of medical imaging devices, quantification of liver fibrosis through image processing technology has become feasible. Stacking technology is one of the effective ensemble techniques for potential usage, but precise tuning to find the optimal configuration manually is challenging. Therefore, this paper proposes a novel EVO-MS model-a multiple stacking ensemble learning model optimized by the energy valley optimization (EVO) algorithm to select most informatic features for fibrosis quantification. Liver contours are profiled from 415 biopsied proven CT cases, from which 10 shape features are calculated and inputted into a Support Vector Machine (SVM) classifier to generate the accurate predictions, then the EVO algorithm is applied to find the optimal parameter combination to fuse six base models: K-Nearest Neighbors (KNNs), Decision Tree (DT), Naive Bayes (NB), Extreme Gradient Boosting (XGB), Gradient Boosting Decision Tree (GBDT), and Random Forest (RF), to create a well-performing ensemble model. Experimental results indicate that selecting 3-5 feature parameters yields satisfactory results in classification, with features such as the contour roundness non-uniformity (Rmax), maximum peak height of contour (Rp), and maximum valley depth of contour (Rm) significantly influencing classification accuracy. The improved EVO algorithm, combined with a multiple stacking model, achieves an accuracy of 0.864, a precision of 0.813, a sensitivity of 0.912, a specificity of 0.824, and an F1-score of 0.860, which demonstrates the effectiveness of our EVO-MS model in staging the degree of liver fibrosis.

Effectiveness of guselkumab in patients with moderate-to-severe plaque psoriasis: a retrospective study from China.

Data on guselkumab as treatment for moderate-to-severe plaque psoriasis, especially in different body regions, in China is limited. This study aimed to estimate the effectiveness of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis, including effectiveness at different body regions. This multicentre, observational study retrospectively enrolled patients with moderate-to-severe plaque psoriasis. Effectiveness outcome was based on Psoriasis Area and Severity Index (PASI) response and improvement in Body Surface Area (BSA) and Dermatology Life Quality Index (DLQI). A total of 51 patients were included, with a median age of 44.00 (18.00, 74.00) years and median duration of psoriasis of 10.00 (0.50, 55.00) years. After 20 weeks of treatment, PASI response with 75% improvement from baseline (PASI 75) was reported in 96.1% of patients; 72.5% of patients achieved a DLQI score of 0-1 at week 20. The percentage of affected BSA was significantly decreased at week 4 (p<0.05), week 12 (p<0.001) and week 20 (p<0.001). PASI score significantly changed from baseline after four weeks (p<0.001), 12 weeks (p<0.001) and 20 weeks of treatment (p<0.001). DLQI score significantly increased at week 4 (p<0.001), week 12 (p<0.001) and week 20 (p<0.001). PASI 75 was achieved for the upper limbs in all cases and 100% PASI improvement (PASI 100) in 89.1%. The head and lower limbs were the areas least responsive to treatment, with PASI 100 achieved in only 68.6% and 70.6%, respectively. Guselkummab provided rapid and sustained PASI improvement, especially for the skin of the upper limbs and body trunk.

Tool mark prediction on the surface of large-aperture mirrors via magnetorheological finishing.

The magnetorheological finishing (MRF) of surfaces often results in tool mark errors. A prediction model can effectively guide subsequent processing, necessitating thorough research. To address this issue, this paper introduces an enhanced continuous tool influence function method. This method involves sub dwell time convolution with varying tool influence functions, enabling tool mark prediction. Numerical simulations demonstrate the proposed method's effectiveness, while the data size is estimated to confirm its economic properties. Subsequently, a MRF experiment was conducted, affirming the practicability through power spectral density evaluation. A fast algorithm is given to guide tool mark predictions on large-aperture mirrors fabrication engineering subjected to sub-aperture polishing.

Evolution mechanism of scratch removal based on the implementation of magnetorheological finishing.

Scratches on optical components induce laser damage and limit the increase in laser power. Magnetorheological finishing (MRF) is a highly deterministic optical manufacturing technology that can improve the surface roughness of optical components. Although MRF has exhibited significant potential for reducing subsurface damage and removing scratches, the principle and mechanism behind the scratch removal are not sufficiently understood. In this study, the theory of fluid mechanics is used to analyze the pressure, velocity, and particle trajectory distribution near a scratch. A physical model was developed for the differential removal of scratches at the bottom and surface of the optical components. The morphological evolution of the scratch was predicted during removal, and detailed experiments were performed to verify the effectiveness of the proposed model. The results indicate that scratches expand laterally rather than being completely removed. Furthermore, scratch removal efficiency is greater when the removal direction is perpendicular to the scratch rather than being parallel. This study offers an intrinsic perspective for a comprehensive understanding of the MRF technique used for scratch removal, which can be beneficial for removing scratches from aspherical optical systems.

Artificial Intelligence-Driven Platform: Unveiling Critical Hepatic Molecular Alterations in Hepatocellular Carcinoma Development.

Since most Hepatocellular Carcinoma (HCC) typically arises as a consequence of long-term liver damage, the hepatic molecular characteristics are closely related to the occurrence of HCC. Gaining comprehensive information about the location, morphology, and hepatic molecular alterations related to HCC is essential for accurate diagnosis. However, there is a dearth of technological advancements capable of concurrently providing precise HCC diagnosis and discerning the accompanying hepatic molecular alterations. In this study, an integrated information system is developed for the pathological-level diagnosis of HCC and the revelation of critical molecular alterations in the liver. This system utilizes computed tomography/Surface-enhanced Raman scattering combined with an artificial intelligence strategy to establish connections between the occurrence of HCC and alterations in hepatic biomolecules. Employing artificial intelligence techniques, the SERS spectra from both healthy and HCC groups are successfully classified into two distinct categories with a remarkable accuracy rate of 91.38%. Based on molecular profiling, it is identified that the nucleotide-to-lipid signal ratio holds significant potential as a reliable indicator for the occurrence of HCC, thereby serving as a promising tool for prevention and therapeutic surveillance.

Comparison of the efficacy of the convex side short fusion combined with concave side single growing rod technique and the traditional bilateral growing rod technique in the treatment of early onset scoliosis.

OBJECTIVES: The application of a growing rod technique can retain the growth and development potential of the spine and thorax while controlling the progression of scoliosis deformity. Theoretically, convex side short fusion combined with a concave side single growing rod technique can significantly reduce the asymmetric growth of the spine in the vertex region in most patients. However, the final clinical outcome of various techniques is yet to be clearly determined and compared between studies. Therefore, we compared the efficacy of these two growing rod techniques in treating early onset scoliosis. METHODS: In a retrospective study of 152 EOS patients seen between 2013.1 and 2019.12, 36 cases of EOS patients were selected for inclusion. Among the 36 cases, 11 cases were treated with convex side short fusion combined with a concave side single growing rod technique, group (A) The remaining 25 cases were treated with traditional bilateral growing rod technique, group (B) Age, gender, etiology, follow-up time, Cobb angle of main curve, T1-S1 height, coronal trunk shift, sagittal vertical axis (SVA), Cobb angle of thoracic kyphosis at last follow-up, and Cobb angle at proximal junction kyphosis of the first and last post-operation follow-up were recorded. In addition, internal fixation related complications, infection, nervous system complications were recorded as well. RESULTS: There was no statistically significant difference between group A and group B in preoperative age, Cobb angle of main curve, coronal trunk shift, T1-S1 height, SVA, Cobb angle of thoracic kyphosis (p > 0.05). However, at the last follow-up (Group A, mean 4.4 ± 1.01 years; Group B, mean 3.6 ± 0.01 years) the Cobb angle of the main curve was less and T1-S1 height greater in group A compared with group B (p < 0.05). There was no statistically significant difference between group A and group B in the correction rate of the Cobb angle of the main curve or the growth rate of T1-S1 height (p > 0.05). There was no statistically significant difference in the coronal imbalance ratio, thoracic kyphosis abnormality ratio, or the occurrence PJK ratio between group A and group B at the last follow-up (p > 0.05), but the sagittal imbalance ratio and internal fixation abnormality ratio were higher in group A than in the group B (p < 0.05). CONCLUSIONS: During the treatment of EOS, both the convex side short fusion combined with concave side single growing rod technique and traditional bilateral growing rod technique can correct the Cobb angle of main curve with no significant hindering of the spinal growth observed. The traditional bilateral growing rod technique has advantages in control of the sagittal balance of the spine, and the complications associated with internal fixation were lower.

Network pharmacology and experimental evidence: ERK/CREB/BDNF signaling pathway is involved in the antidepressive roles of Kaiyu Zhishen decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication. However, the standalone antidepressant efficacy of KZD and its underlying mechanisms merit in-depth investigation. AIM OF THE STUDY: This research aims to elucidate the impact of KZD on MDD and delineate its mechanistic pathways through integrated network pharmacological assessments and empirical in vitro and in vivo analyses. MATERIALS AND METHODS: To ascertain the optimal antidepressant dosage and mechanism of KZD, a Chronic Unpredictable Mild Stress (CUMS)-induced depression model in mice was established to evaluate depressive behaviors. High-Performance Liquid Chromatography (HPLC) and network pharmacological approaches were employed to predict KZD's antidepressant mechanisms. Subsequently, hippocampal samples were subjected to 4D-DIA proteomic sequencing and validated through Western blot, immunofluorescence, Nissl staining, and pathway antagonist applications. Additionally, cortisol-stimulated PC12 cells were utilized to simulate neuronal damage, analyzing protein and mRNA levels of MAPK-related signals and cell proliferation markers. RESULTS: The integration of network pharmacology and HPLC identified kaempferol and quercetin as KZD's principal active compounds for MDD treatment. Proteomic and network pharmacological KEGG pathway analyses indicated the MAPK signaling pathway as a critical regulatory mechanism for KZD's therapeutic effect on MDD. KZD was observed to mitigate CUMS-induced upregulation of p-ERK/ERK, CREB, and BDNF protein expressions in hippocampal cells by attenuating oxidative stress, thereby ameliorating neuronal damage and exerting antidepressant effects. The administration of PD98059 counteracted KZD's improvements in depression-like behaviors and downregulated p-ERK/ERK and BDNF protein expressions in the hippocampus. CONCLUSIONS: This investigation corroborates KZD's pivotal, dose-dependent role in antidepressant activity. Both in vivo and in vitro experiments demonstrate KZD's capacity to modulate the ERK-CREB-BDNF signaling pathway by diminishing ROS expression induced by oxidative stress, enhancing neuronal repair, and thus, manifesting antidepressant properties. Accordingly, KZD represents a promising herbal candidate for further antidepressant research.

Complete genome assembly provides a high-quality skeleton for pan-NLRome construction in melon.

Melon (Cucumis melo L.), being under intensive domestication and selective breeding, displays an abundant phenotypic diversity. Wild germplasm with tolerance to stress represents an untapped genetic resource for discovery of disease-resistance genes. To comprehensively characterize resistance genes in melon, we generate a telomere-to-telomere (T2T) and gap-free genome of wild melon accession PI511890 (C. melo var. chito) with a total length of 375.0 Mb and a contig N50 of 31.24 Mb. The complete genome allows us to dissect genome architecture and identify resistance gene analogs. We construct a pan-NLRome using seven melon genomes, which include 208 variable and 18 core nucleotide-binding leucine-rich repeat receptors (NLRs). Multiple disease-related transcriptome analyses indicate that most up-regulated NLRs induced by pathogens are shell or cloud NLRs. The T2T gap-free assembly and the pan-NLRome not only serve as essential resources for genomic studies and molecular breeding of melon but also provide insights into the genome architecture and NLR diversity.

Characterization of the biological and transcriptomic landscapes of bone marrow-derived mesenchymal stem cells in patients with multiple myeloma.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) have been acknowledged as the most important stromal cells in the bone marrow (BM) microenvironment for physiologic hematopoiesis and the concomitant hematologic malignancies. However, the systematic and detailed dissection of the biological and transcriptomic signatures of BM-MSCs in multiple myeloma (MM) are largely unknown. METHODS: In this study, we isolated and identified BM-MSCs from 10 primary MM patients and 10 healthy donors (HD). On the one hand, we compared the multifaceted biological characteristics of the indicated two BM-MSCs, including biomarker expression pattern, multilineage differentiation potential, stemness and karyotyping, together with the cellular vitality and immunosuppressive property. On the other hand, we took advantage of RNA-SEQ and bioinformatics analysis to verify the similarities and differences at the transcriptomic level between MM-MSCs and HD-MSCs. RESULTS: As to biological phenotypes and biofunctions, MM-MSCs revealed conservation in immunophenotype, stemness and differentiation towards adipocytes and chondrocytes with HD-MSCs, whereas with impaired osteogenic differentiation potential, cellular vitality and immunosuppressive property. As to transcriptomic properties, MM-MSCs revealed multidimensional alterations in gene expression profiling and genetic variations. CONCLUSIONS: Overall, our date systematic and detailed reflected the multifaceted similarities and variations between MM-MSCs and HD-MSCs both at the cellular and molecular levels, and in particular, the alterations of immunomodulation and cellular viability of MM-MSCs, which wound benefit the further exploration of the pathogenesis and new drug application (NDA) of multiple myeloma from the view of BM-MSCs.

Ultrasensitive and Multiple Biomarker Discrimination for Alzheimer's Disease via Plasmonic & Microfluidic Sensing Technologies.

As the population ages, the worldwide prevalence of Alzheimer's disease (AD) as the most common dementia in the elderly is increasing dramatically. However, a long-term challenge is to achieve rapid and accurate early diagnosis of AD by detecting hallmarks such as amyloid beta (Aß42). Here, a multi-channel microfluidic-based plasmonic fiber-optic biosensing platform is established for simultaneous detection and differentiation of multiple AD biomarkers. The platform is based on a gold-coated, highly-tilted fiber Bragg grating (TFBG) and a custom-developed microfluidics. TFBG excites a high-density, narrow-cladding-mode spectral comb that overlaps with the broad absorption of surface plasmons for high-precision interrogation, enabling ultrasensitive monitoring of analytes. In situ detection and in-parallel discrimination of different forms of Aß42 in cerebrospinal fluid (CSF) are successfully demonstrated with a detection of limit in the range of ≈30-170 pg mL-1, which is one order of magnitude below the clinical cut-off level in AD onset, providing high detection sensitivity for early diagnosis of AD. The integration of the TFBG sensor with multi-channel microfluidics enables simultaneous detection of multiple biomarkers using sub-µL sample volumes, as well as combining initial binding rate and real-time response time to differentiate between multiple biomarkers in terms of binding kinetics. With the advantages of multi-parameter, low consumption, and highly sensitive detection, the sensor represents an urgently needed potentials for large-scale diagnosis of diseases at early stage.

Catalytic oxidation of toluene by manganese oxides: Effect of K+ doping on oxygen vacancy.

Alkali metal potassium was beneficial to the electronic regulation and structural stability of transition metal oxides. Herein, K ions were introduced into manganese oxides by different methods to improve the degradation efficiency of toluene. The results of activity experiments indicated that KMnO4-HT (HT: Hydrothermal method) exhibited outstanding low-temperature catalytic activity, and 90% conversion of toluene can be achieved at 243°C, which was 41°C and 43°C lower than that of KNO3-HT and Mn-HT, respectively. The largest specific surface area was observed on KMnO4-HT, facilitating the adsorption of toluene. The formation of cryptomelane structure over KMnO4-HT could contribute to higher content of Mn3+ and lattice oxygen (Olatt), excellent low-temperature reducibility, and high oxygen mobility, which could increase the catalytic performance. Furthermore, two distinct degradation pathways were inferred. Pathway Ⅰ (KMnO4-HT): toluene → benzyl → benzoic acid → carbonate → CO2 and H2O; Pathway ⅠⅠ (Mn-HT): toluene → benzyl alcohol → benzoic acid → phenol → maleic anhydride → CO2 and H2O. Fewer intermediates were detected on KMnO4-HT, indicating its stronger oxidation capacity of toluene, which was originated from the doping of K+ and the interaction between KOMn. More intermediates were observed on Mn-HT, which can be attributed to the weaker oxidation ability of pure Mn. The results indicated that the doping of K+ can improve the catalytic oxidation capacity of toluene, resulting in promoted degradation of intermediates during the oxidation of toluene.

Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors.

The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.