Biosynthesis of silver nanoparticles using Burkholderia contaminans ZCC and mechanistic analysis at the proteome level.

The biogenic synthesis of silver nanoparticles (AgNPs) by microorganisms has been a subject of increasing attention. Despite extensive studies on this biosynthetic pathway, the mechanisms underlying the involvement of proteins and enzymes in AgNPs production have not been fully explored. Herein, we reported that Burkholderia contaminans ZCC was able to reduce Ag+ to AgNPs with a diameter of (10±5) nm inside the cell. Exposure of B. contaminans ZCC to Ag+ ions led to significant changes in the functional groups of cellular proteins, with approximately 5.72% of the (C-OH) bonds being converted to (C-C/C-H) (3.61%) and CO (2.11%) bonds, and 4.52% of the CO (carbonyl) bonds being converted to (C-OH) bonds. Furthermore, the presence of Ag+ and AgNPs induced the ability of extracellular electron transfer for ZCC cells via specific membrane proteins, but this did not occur in the absence of Ag+ ions. Proteomic analysis of the proteins and enzymes involved in heavy metal efflux systems, protein secretion system, oxidative phosphorylation, intracellular electron transfer chain, and glutathione metabolism suggests that glutathione S-transferase and ubiquinol-cytochrome c reductase iron-sulfur subunit play importance roles in the biosynthesis of AgNPs. These findings contribute to a deeper understanding of the functions exerted by glutathione S-transferase and ferredoxin-thioredoxin reductase iron-sulfur subunits in the biogenesis of AgNPs, thereby hold immense potential for optimizing biotechnological techniques aimed at enhancing the yield and purity of biosynthetic AgNPs.

Multiplexed representation of others in the hippocampal CA1 subfield of female mice.

Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.

Widely targeted metabolomics reveals differences in metabolites of Paeonia lactiflora cultivars.

INTRODUCTION: Paeonia lactiflora contains diverse active constituents and exhibits various pharmacological activities. However, only partial identification of biologically active substances from P. lactiflora has been achieved using low-throughput techniques. Here, the roots of P. lactiflora, namely, Fenyunu (CK), Dafugui (DFG), and Red Charm (HSML), were studied. The primary and secondary metabolites were investigated using ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESIMS/MS). METHODS: The chemical compounds and categories were detected using broadly targeted UPLC-MS/MS. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and hierarchical clustering analysis (HCA) were carried out for metabolites of different varieties of P. lactiflora. RESULTS: A total of 1237 compounds were detected and classified into 11 categories. HCA, PCA, and OPLS-DA of these metabolites indicated that each variety of P. lactiflora was clearly separated from the other groups. Differential accumulated metabolite analysis revealed that the three P. lactiflora varieties contained 116 differentially activated metabolites (DAMs) involved in flavonoid, flavone, and flavonol metabolism. KEGG pathway analysis revealed that, in 65 pathways, 336 differentially abundant metabolites (DMs) were enriched in the CK and DFG groups; moreover, the type and content of terpenoids were greater in the CK group than in the DFG group. The CK and HSML groups contained 457 DMs enriched in 61 pathways; the type and amount of flavonoids, terpenoids, and tannins were greater in the CK group than in the HSML group. The DFG and HSML groups contained 497 DMs enriched in 65 pathways; terpenoids and alkaloids were more abundant in the HSML variety than in the DFG variety. CONCLUSIONS: A total of 1237 compounds were detected, and the results revealed significant differences among the three P. lactiflora varieties. Among the three P. lactiflora varieties, phenolic acids and flavonoids composed the largest and most diverse category of metabolites, and their contents varied greatly. Therefore, CK is suitable for medicinal plant varieties, and DFG and HSML are suitable for ornamental plant varieties. Twelve proanthocyanidin metabolites likely determined the differences in color among the three varieties.

Unusual Case of Esophageal Foreign Body: A Whole Mantis Shrimp.

Esophageal foreign bodies (FBs) are one of the common emergencies in otolaryngology, usually involving objects accidentally swallowed, and generally do not result in severe respiratory distress. This article presents an extremely rare case of an esophageal FB, where a 44-year-old man accidentally ingested an entire mantis shrimp while sucking its flavored tail, and was sent to the emergency department for severe throat pain and difficulty breathing. We immediately performed a laryngoscopy that revealed the FB that obstructs the entrance of the esophagus, obstructing the glottis due to the long shape of the shrimp. The mantis shrimp had barbs on its shell and trying to remove it intact would cause significant damage to the pharyngeal mucosa. Therefore, we extracted the mantis shrimp in segments under general anesthesia and applied electrocoagulation to stop bleeding from the damaged and bleeding posterior pharyngeal mucosa. As an esophagography was performed the following day, there were no signs of esophageal perforation. Through the detailed description and analysis of this case, our aim is to raise clinical awareness among physicians of such rare occurrences. Most important, appropriate examination and procedures of FBs should be performed based on the type, shape, and location of the FB.

Performance, kinetic characteristics and bacterial community of short-cut nitrification and denitrification system at different ferrous ion conditions.

In order to explore the operation performance, kinetic characteristics and bacterial community of the short-cut nitrification and denitrification (SND) system, the SND system with pre-cultured short cut nitrification and denitrification sludge was established and operated under different ferrous ion (Fe (II)) conditions. Experimental results showed that the average NH4+-N removal efficiency (ARE) of SND system was 97.3% on Day 5 and maintained a high level of 94.9% ± 1.3% for a long operation period. When the influent Fe(II) concentration increased from 2.3 to 7.3 mg L-1, the sedimentation performance, sludge concentration and organic matter removal performance were improved. However, higher Fe(II) of 12.3 mg L-1 decreased the removal of nitrogen and CODCr with the relative abundance (RA) of Proteobacteria and Bacteroidetes decreased to 30.28% and 19.41%, respectively. Proteobacteria, Bacteroidetes and Firmicutes were the dominant phyla in SND system. Higher Fe(II) level of 12.3 mg L-1 increase the RA of denitrifying genus Trichococcus (33.93%), and the denitrifying genus Thauera and Tolumonas dominant at Fe(II) level of no more than 7.3 mg L-1.

GmMYB114 Facilitates the Synthesis of Anthocyanins in Soybean Sprouts under Blue Light.

Soybean sprouts constitute a significant segment of the vegetable market due to their nutritional richness, particularly in various flavonoids, which contribute to numerous health benefits. The augmentation of the flavonoid content in soybean sprouts is pivotal for enhancing their economic value. While research has established the potential of blue light in promoting the synthesis of anthocyanins, a subclass of flavonoids known for their health advantages, the precise regulatory mechanisms remain elusive. In this study, we identified a notable upregulation of an R2R3 type MYB transcription factor, GmMYB114, in response to blue light exposure, exhibiting a significant positive correlation with anthocyanin accumulation in soybean sprouts. The functional role of GmMYB114 was validated in soybean hairy roots, wherein its overexpression substantially augmented anthocyanin synthesis. Further investigations employing yeast one-hybrid (Y1H), dual-luciferase reporter (LUC), and GUS assays revealed that GmMYB114 indirectly influences anthocyanin synthesis as it does not directly bind to the promoters of anthocyanin synthesis genes to activate their expression. These findings contribute to elucidating the mechanism underlying blue light-mediated enhancement of anthocyanin synthesis in soybean sprouts, offering valuable insights for harnessing molecular technologies to obtain anthocyanin-enriched soybean sprouts.

High-performance Pyroelectric Property Accompanied by Spin Crossover in a Single Crystal of Fe(II) Complex.

Pyroelectric materials hold significant potential for energy harvesting, sensing, and imaging applications. However, achieving high-performance pyroelectricity across a wide temperature range near room temperature remains a significant challenge. Herein, we demonstrate a single crystal of Fe(II) spin-crossover compound shows remarkable pyroelectric properties accompanied by a thermally controlled spin transition. In this material, the uniaxial alignment of polar molecules results in a polarization of the lattice. As the molecular geometry is modulated during a gradual spin transition, the polar axis experiences a colossal thermal expansion with a coefficient of 796×10-6 K-1. Consequently, the material's polarization undergoes significant modulation as a secondary pyroelectric effect. The considerable shift in polarization (pyroelectric coefficient, p=3.7-22 nC K-1cm-2), coupled with a low dielectric constant (ϵ'=4.4-5.4) over a remarkably wide temperature range of 298 to 400 K, suggests this material is a high-performance pyroelectric. The demonstration of pyroelectricity combined with magnetic switching in this study will inspire further investigations in the field of molecular electronics and magnetism.

Clinical efficacy analysis of surgical treatment for spinal metastasis under the multidisciplinary team using the NOMS decision system combined with the revised Tokuhashi scoring system: a randomized controlled study.

OBJECTIVE: Despite advancements in spinal metastasis surgery techniques and the rapid development of multidisciplinary treatment models, we aimed to explore the clinical efficacy of spinal metastasis surgery performed by a combined NOMS decision system-utilizing multidisciplinary team and Revised Tokuhashi scoring system, compared with the Revised Tokuhashi scoring system. METHODS: Clinical data from 102 patients with spinal metastases who underwent surgery at three affiliated hospitals of Zunyi Medical University from December 2017 to June 2022 were analysed. The patients were randomly assigned to two groups: 52 patients in the treatment group involving the combined NOMS decision system-utilizing multidisciplinary team and Revised Tokuhashi scoring system (i.e., the combined group), and 50 patients in the treatment group involving the Revised Tokuhashi scoring system only (i.e., the revised TSS-only group). Moreover, there were no statistically significant differences in preoperative general data or indicators between the two groups. Intraoperative and postoperative complications, average hospital stay, mortality rate, and follow-up observation indicators, including the visual analogue scale (VAS) score for pain, Eastern Cooperative Oncology Group (ECOG) performance status, Karnofsky Performance Status (KPS) score, negative psychological assessment score (using the Self-Rating Anxiety Scale, [SAS]), and neurological function recovery score (Frankel functional classification) were compared between the two groups. RESULTS: All 102 patients successfully completed surgery and were discharged. The follow-up period ranged from 12 to 24 months, with an average of (13.2 ± 2.4) months. The patients in the combined group experienced fewer complications such as surgical wound infections 3 patients(5.77%), intraoperative massive haemorrhage 2 patients(3.85%), cerebrospinal fluid leakage 2 patients(3.85%), deep vein thrombosis 4 patients(7.69%),and neurological damage 1 patient(1.92%), than patients in the revised TSS-only group (wound infections,11 patients(22%); intraoperative massive haemorrhage, 8 patients(16%);cerebrospinal fluid leakage,5 patients(10%);deep vein thrombosis,13 patients (26%); neurological damage,2 patients (4%). Significant differences were found between the two groups in terms of surgical wound infections, intraoperative massive haemorrhage, and deep vein thrombosis (P < 0.05). The average postoperative hospital stay in the combined group (7.94 ± 0.28 days) was significantly shorter than that in the revised TSS-only group (10.33 ± 0.30 days) (P < 0.05). Long-term follow-up (1 month, 3 months, 6 months, and 1 year postoperatively) revealed better clinical outcomes in the combined group than in the revised TSS-only group in terms of VAS scores, overall KPS%, neurological function status Frankel classification, ECOG performance status, and SAS scores.(P < 0.05). CONCLUSION: A multidisciplinary team using the NOMS combined with the Revised Tokuhashi scoring system for spinal metastasis surgery showed better clinical efficacy than the sole use of the Revised Tokuhashi scoring system. This personalized, precise, and rational treatment significantly improves patient quality of life, shortens hospital stay, reduces intraoperative and postoperative complications, and lowers mortality rates.

Modified ZIF-8 Nanoparticles for Targeted Metabolic Treatment of Acute Spinal Cord Injury.

The activation of proinflammatory M1-type macrophages in the injured lesion accelerates the progression of a spinal cord injury (SCI). However, adverse side effects during systemic treatments targeting M1 macrophages have limited their applications. Nanoplatforms are novel carriers of traditional Chinese medicine because of their great efficiency to deliver and accumulation in the lesion. Herein, we synthesized a modified zeolitic imidazolate framework-8 (ZIF-8) nanoplatform for internalization and accumulation in the injured spinal cord and effective administration for SCI. In vitro and in vivo experiments suggested that Prussian blue and Schisandrin B modified ZIF-8 effectively accumulated in M1 macrophages, inhibited reactive oxygen species (ROS), and polarized the macrophage from proinflammatory M1 to anti-inflammatory M2 for rapid tissue infiltration by reprogramming the metabolic macrophages phenotype. This nanoplatform achieves a synergistic therapeutic effect of immunomodulation and neuroprotection, thereby shedding new light on the application of ZIF-8, and provides great potential for SCI.

ERK/STAT3 activation through CCL17/CCR4 axis-mediated type 2 cytokine-involved signaling pathways in Th2 cells regulates cutaneous drug reactions.

Cutaneous drug reactions (CDRs) are common drug-induced allergic reactions that cause severe consequences in HIV/AIDS patients. The CCL17/CCR4 axis is involved in the immune mechanism of allergic diseases, but its role in the CDRs has not been determined. Here, we aimed to determine the role of the CCL17/CCR4 axis and the underlying mechanism involved in CDRs. In this study, the serum cytokine levels in patients with CDR and healthy controls were measured. The CCL17-triggered allergic profile was screened via a PCR array. Apoptosis of keratinocytes cocultured with CCL17-stimulated Th2 cells was analyzed by flow cytometry. An NVP-induced rat CDR model was established, and dynamic inflammatory factor levels and Th2 cells in the peripheral blood of the rats were measured. Rat skin lesions and signaling pathways in Th2 cells were also analyzed. We showed that the serum CCL17 level was significantly upregulated in CDR patients (P = 0.0077), and the Th2 cell subgroup was also significantly elevated in the CDR rats. The CCL17/CCR4 axis induces Th2 cells to release IL-4 and IL-13 via the ERK/STAT3 pathway. The CCR4 antagonist compound 47 can alleviate rash symptoms resulting from NVP-induced drug eruption, Th2 cell subgroup, IL-4, and IL-13 and inhibit keratinocyte apoptosis. Taken together, these findings indicate that the CCL17/CCR4 axis mediates CDR via the ERK/STAT3 pathway in Th2 cells and type 2 cytokine-induced keratinocyte apoptosis.

Localized Temperature Engineering Enables Writing of Heterostructures in Glass for Polarized Photoluminescence of Perovskites.

Metal halide perovskite (MHP) structures that exhibit polarized photoluminescence (PL) have attracted significant interest in fabricating light field regulation elements for display, imaging, and information storage applications. We report a three-dimensional direct lithography of heterostructures for controllable polarized PL inside glass by laser-induced localized temperature engineering. The heterostructures consisted of oriented periodic structures (OPSs) and MHP nanocrystals, and the mechanism for hierarchical distribution of heterostructures was illustrated. The patterning of heterostructures for manipulable polarized PL can be used for information encryption, wave-plate, and polarized micro-LEDs.

Synthesis of Fluorine-Containing Multisubstituted Oxa-Spiro[4,5]cyclohexadienones via a Fluorinated Alcohol-Catalyzed One-Pot Sequential Cascade Strategy.

In recent years, the application of fluorinated alcohols as solvents, cosolvents, or additives has become important in modern organic synthesis. However, their potential as efficient catalysts in organic synthesis has not been well-explored. In this article, we report on the development of a one-pot sequential cascade reaction of p-quinone methides with difluoroenoxysilanes using hexafluoroisopropanol as catalyst. This reaction allows for the preparation of fluorinated multisubstituted oxa-spiro[4,5]cyclohexadienones. By using 50 mol % 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP), the reaction proceeds smoothly to yield 1,6-conjugated products, which are then subjected to oxidative dearomatization/hemiacetalization using PhI(OAc)2. The overall process affords moderate to high yields and excellent diastereoselectivities.

STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking.

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME. We found that schizophrenia-related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia-like behaviors. Moreover, among seven antipsychotic drugs, patients with the C-C (307Pro-851Ala) haplotype responded better to haloperidol than did the T-A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophrenia-related STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.

Numerical study of the plasmonic slab lens for improving direct-write nano lithography.

Plasmonic direct-write lithography (PDWL) provides a potential tool for the fabrication and manufacturing at the nano scale due to its high-resolution and low-cost. However, the shallow exposure depth hinders its practical application. Here, we incorporate the plasmonic slab lenses (PSLs) into PDWL to amplify and compensate evanescent waves, leading to improved light intensity, depth, resolution and better tolerance to the air gap beyond the near field optical lithography. Two typical plasmonic probes with different nanostructure and localized plasmonic resonance mechanisms are designed and fabricated as representatives, the local intensity enhancement of which mainly depend on the oscillations of transverse and longitudinal electric field components, respectively. Optimizations considering the PSL structure, material and the illuminating wavelength are performed to amplify different field components and figure out the best lithography configuration. Simulation results indicate that Ag-Ag cavity PSL and 355 nm illumination is the best combination for the lithography with bowknot aperture probe, while the semi-ring probe exhibits better performance under the condition of Ag-Al cavity PSL and 405 nm illumination. The semi-ring probe in combination with a plasmonic cavity, for instance, is demonstrated to enhance the light intensity by 4 times at the bottom layer of the photoresist compared to that without PSL and realize a lithography resolution of 23 nm. Our scheme is believed to boost the application of PDWL as a high-resolution and low-cost nanofabrication technology, and it may even serve as an alternative for the high-cost scanning method, such as focused ion beam and electron beam lithography.

Comparative study of abdominal CT enhancement in overweight and obese patients based on different scanning modes combined with different contrast medium concentrations.

PURPOSE: To compare image quality, iodine intake, and radiation dose in overweight and obese patients undergoing abdominal computed tomography (CT) enhancement using different scanning modes and contrast medium. METHODS: Ninety overweight and obese patients (25 kg/m2≤body mass index (BMI)<  30 kg/m2 and BMI≥30 kg/m2) who underwent abdominal CT-enhanced examinations were randomized into three groups (A, B, and C) of 30 each and scanned using gemstone spectral imaging (GSI) +320 mgI/ml, 100 kVp + 370 mgI/ml, and 120 kVp + 370 mgI/ml, respectively. Reconstruct monochromatic energy images of group A at 50-70 keV (5 keV interval). The iodine intake and radiation dose of each group were recorded and calculated. The CT values, contrast-to-noise ratios (CNRs), and subjective scores of each subgroup image in group A versus images in groups B and C were by using one-way analysis of variance or Kruskal-Wallis H test, and the optimal keV of group A was selected. RESULTS: The dual-phase CT values and CNRs of each part in group A were higher than or similar to those in groups B and C at 50-60 keV, and similar to or lower than those in groups B and C at 65 keV and 70 keV. The subjective scores of the dual-phase images in group A were lower than those of groups B and C at 50 keV and 55 keV, whereas no significant difference was seen at 60-70 keV. Compared to groups B and C, the iodine intake in group A decreased by 12.5% and 13.3%, respectively. The effective doses in groups A and B were 24.7% and 25.8% lower than those in group C, respectively. CONCLUSION: GSI +320 mgI/ml for abdominal CT-enhanced in overweight patients satisfies image quality while reducing iodine intake and radiation dose, and the optimal keV was 60 keV.

Liberal surgical laparoscopy reduction for acute intussusception: experience from a tertiary pediatric institute.

The optimal treatment for acute intussusception has not yet been defined. In this study, we explored whether employing a liberal laparoscopic intervention for intussusception could lead to favorable outcomes. We performed a historical control analysis to evaluate the outcomes associated with this liberal surgical management protocol. This liberal surgical management protocol were revised to incorporate a new protocol centered around the laparoscopic approach. In some cases of acute intussusception, liberal laparoscopic exploration and intervention were undertaken without initial hydrostatic or pneumatic reduction. During the study interval, a retrospective review was conducted on a total of 3086 patients. These were categorized into two groups: 1338 cases before May 2019 (pre-protocol group) and 1748 cases after May 2019 (post-protocol group). Surgical intervention rates in the pre-protoco and post-protocol period were 10.2% and 27.4% respectively (odds ratio [OR] = 0.30 [95% CI 0.25-0.37]; p < 0.001). No significant differences were observed in baseline clinical characteristics or demographic features between the two groups. The duration from admission to operation was longer for the pre-protocol group (p = 0.008) than for the post-protocol group. The post-protocol group demonstrated decreases in both intestinal resection (OR = 1.50 [95% CI 0.96-2.35]; p = 0.048) and total recurrent events (OR = 1.27 [95% CI 1.04-1.55]; p = 0.012) compared to the pre-protocol group. Liberal laparoscopic intervention for intussusception may effectively reduce the risk of intestinal resection and total recurrent events, thereby exhibiting promising outcomes for patients with intussusception.

Induced Decomposition and Slip Interface Transformation of Oleic Acid Enables Ultralow Wear in Boundary Lubrication.

The tribological behavior of carboxylic acids, especially oleic acid, in boundary lubrication conditions is a subject of interest. This study presents the results of four-ball tribological tests conducted under varying contact pressures and sliding speeds. The findings reveal a critical turning speed within a confined zone, which causes a significant change in the frictional performances of oleic acid, leading to the formation of an ultralow wear tribofilm. This tribofilm, predominantly composed of oxyhydrogen compounds and hydrocarbons with more than five carbon atoms, is generated by the molecular action of oleic acid. Reactive nonequilibrium molecular dynamics simulations demonstrate that the shear speed-dependent decomposition modes of oleic acid and the transformation of the lubrication slip interface are the fundamental processes underlying the formation of this ultralow-wear boundary tribofilm.

Tumor microenvironment-activated theranostic nanozymes for trimodal imaging-guided combined therapy.

Synergistic therapy is expected to be a promising strategy for highly effective cancer treatment. However, the rational design of a simple and multifunctional nanoplatform still remains a grand challenge. Considering the nature of weak acidic, hypoxic, and H2O2 abundant tumor microenvironment, we constructed an indocyanine green (ICG) modified platinum nanoclusters (Pt NCs) decorated gold nanobipyramids (Au NBPs) to form the multifunctional nanocomposites (Au NBPs@Pt NCs-ICG) for multimodal imaging mediated phototherapy and chemodynamic cancer therapy. The photosensitizer ICG was covalently linked to Au NBPs@Pt NCs by bridging molecules of SH-PEG-NH2 for both photodynamic therapy (PDT) and fluorescence imaging. Besides, Au NBPs@Pt NCs-ICG nanocomposites exhibited catalase- and peroxidase-like activities to generate O2 and ·OH, which relieved the tumor hypoxia and upregulated antitumoral ROS level. Moreover, the combination of Au NBPs and ICG endowed the Au NBPs@Pt NCs-ICG with super photothermal conversion for effective photothermal imaging and therapy. In addition, the Au NBPs@Pt NCs-ICG nanoplatform displayed excellent X-ray computed tomography (CT) imaging ability due to the presence of high-Z elements (Au and Pt). Overall, our results demonstrated that Au NBPs@Pt NCs-ICG nanoplatform exhibited a multimodal imaging guided synergistic PTT/PDT/CDT therapeutic manners and held great potential as an efficient treatment for breast cancer.

PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes.

BACKGROUND: The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking. The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy, intellectual disability/developmental delay, and malformations, such as facial abnormalities. METHODS: We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequencing. Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients. RESULTS: With the inclusion of the newly diagnosed cases in this study, 103 cases with PACS gene family-related neurological diseases were reported, of which 43 were PACS2-related cases and the remaining were PACS1-related cases. Most patients had seizures, which have been reported to be effectively controlled by several types of anti-seizure medications (ASMs). The most efficacious and frequently prescribed ASMs included sodium valproate (43.3%, 13/30), oxcarbazepine/carbamazepine (26.7%, 8/30), and levetiracetam (20%, 6/30). Almost all patients had intellectual disability/developmental delay. The most common pathogenic missense variants were PACS1 p. Arg203Trp and PACS2 p.Glu209Lys. In addition, we report a patient carrying a likely pathogenic copy number variation (CNV) (de novo heterozygous deletion of chr14:105821380-106107443, 286 kilobase, destroyed part of the furin-binding region domain and the protein structure after it) with more severe and refractory late-onset epilepsy. CONCLUSIONS: The clinical phenotypes of the different PACS heterozygous missense variants were similar. The pathogenic variant sites of PACS1 and PACS2 were quite limited but located in different regions. A CNV destroying part of the PACS2 gene might also be pathogenic. These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family. Video Abstract (MP4 65767 kb).