25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages.

Macrophages are critical to turn noninflamed "cold tumors" into inflamed "hot tumors". Emerging evidence indicates abnormal cholesterol metabolites in the tumor microenvironment (TME) with unclear function. Here, we uncovered the inducible expression of cholesterol-25-hydroxylase (Ch25h) by interleukin-4 (IL-4) and interleukin-13 (IL-13) via the transcription factor STAT6, causing 25-hydroxycholesterol (25HC) accumulation. scRNA-seq analysis confirmed that CH25Hhi subsets were enriched in immunosuppressive macrophage subsets and correlated to lower survival rates in pan-cancers. Targeting CH25H abrogated macrophage immunosuppressive function to enhance infiltrating T cell numbers and activation, which synergized with anti-PD-1 to improve anti-tumor efficacy. Mechanically, lysosome-accumulated 25HC competed with cholesterol for GPR155 binding to inhibit the kinase mTORC1, leading to AMPKα activation and metabolic reprogramming. AMPKα also phosphorylated STAT6 Ser564 to enhance STAT6 activation and ARG1 production. Together, we propose CH25H as an immunometabolic checkpoint, which manipulates macrophage fate to reshape CD8+ T cell surveillance and anti-tumor response.

An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum.

BACKGROUND: Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum. METHODS: We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4',6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male ß-alanyl-tryptamine (BATT) was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone ß-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes. CONCLUSIONS: We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production.

Insulin receptor participates in the peripheral olfactory processes of honey bees (Apis cerana cerana).

Insulin receptors (InR) are an integral component of the insulin/insulin-like growth factor signaling pathway, which plays a vital role in insect development, lifespan, reproduction, and olfactory sensitivity. However, whether InR participate in the peripheral olfactory system of insects remains unclear. Recently, we found that 2-heptanone (2-HT) affects AcerInR expression, the gene for an InR protein, in Apis cerana cerana. We then examined the spatiotemporal expression profile of the gene in A. cerana cerana. The mRNA of AcerInR was primarily expressed in the antennae, wings, and legs of forager bees, which are probable chemosensory tissues. The results of fluorescence competitive binding assays, combined with site-directed mutagenesis, demonstrated that AcerOBP6 and AcerOBP14 exhibit strong binding affinities to 2-HT. Furthermore, after foragers were fed with double-stranded AcerInR, the expression levels of AcerOBP6 and AcerOBP14 decreased significantly, as did the electroantennogram responsiveness to 2-HT and some other odorants. In conclusion, our findings provide a foundation for understanding the involvement of AcerInR in the odor perception of A. cerana cerana. Moreover, they offer novel insights into the olfactory recognition mechanism in insects.

Research Progress of Vertical Channel Thin Film Transistor Device.

Thin film transistors (TFTs) as the core devices for displays, are widely used in various fields including ultra-high-resolution displays, flexible displays, wearable electronic skins and memory devices, especially in terms of sensors. TFTs have now started to move towards miniaturization. Similarly to MOSFETs problem, traditional planar structure TFTs have difficulty in reducing the channel's length sub-1µm under the existing photolithography technology. Vertical channel thin film transistors (V-TFTs) are proposed. It is an effective solution to overcome the miniaturization limit of traditional planar TFTs. So, we summarize the different aspects of VTFTs. Firstly, this paper introduces the structure types, key parameters, and the impact of different preparation methods in devices of V-TFTs. Secondly, an overview of the research progress of V-TFTs' active layer materials in recent years, the characteristics of V-TFTs and their application in examples has proved the enormous application potential of V-TFT in sensing. Finally, in addition to the advantages of V-TFTs, the current technical challenge and their potential solutions are put forward, and the future development trend of this new structure of V-TFTs is proposed.

The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN-I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25-dihydroxycholesterol (7α, 25-OHC), are identified in SLE patients. The authors find that 7α, 25-OHC binding to its receptor Epstein-Barr virus-induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN-ß, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN-γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2-deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane-induced SLE. Together, via sensing the oxysterol 7α, 25-OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE.

Comprehensive metabolomic and lipidomic alterations in response to heat stress during seed germination and seedling growth of Arabidopsis.

Temperature affects seed germination and seedling growth, which is a critical and complex stage in plant life cycle. However, comprehensive metabolic basis on temperature implicating seed germination and seedling growth remains less known. Here, we applied the high-throughput untargeted metabolomic and advanced shotgun lipidomic approaches to profile the Arabidopsis 182 metabolites and 149 lipids under moderate (22°C, 28°C) and extreme high (34°C, 40°C) temperatures. Our results showed that a typical feature of the metabolism related to organic acids/derivates and amines was obviously enriched at the moderate temperature, which was implicated in many cellular responses towards tricarboxylic acid cycle (TCA), carbohydrates and amino acids metabolism, peptide biosynthesis, phenylpropanoid biosynthesis and indole 3-acetate (IAA) biosynthetic pathway. Whereas, under extreme high temperatures, there was no seed germination, but 148 out of total 182 metabolites were highly enriched, involving in the galactose metabolism, fatty acid degradation, tryptophan/phenylalanine metabolism, and shikimic acid-mediated pathways especially including alkaloids metabolism and glucosinolate/flavone/flavonol biosynthesis. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) also exhibited the gradually increased tendency from moderate temperatures to extreme high temperatures; whereas phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG) were contrary to decrease. Another typical feature of the distinguished metabolites between 22°C and 28°C, the TCA, disaccharides, nucleotides, polypeptides, SQDG and the biosynthesis of fatty acids and glucobrassicin-mediated IAA were obviously decreased at 28°C, while amino acids, trisaccharides, PE, PC, PA, PS, MGDG, DGDG and diacylglycerol (DAG) preferred to enrich at 28°C, which characterized the alteration of metabolites and lipids during fast seedling growth. Taking together, our results provided the comprehensive metabolites phenotyping, revealed the characteristics of metabolites necessary for seed germination and/or seedling growth under different temperatures, and provided insights into the different metabolic regulation of metabolites and lipid homeostasis for seed germination and seedling growth.

Effectiveness of Internet-based cognitive-behavioural therapy for obsessive-compulsive disorder (OCD-NET) and body dysmorphic disorder (BDD-NET) in the Swedish public health system using the RE-AIM implementation framework.

Objectives: Therapist-guided internet-delivered cognitive behaviour therapy (ICBT) is an efficacious treatment for obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD), but it is unclear if the results obtained in controlled trials can be reproduced in clinical settings. We evaluated the implementation of ICBT for OCD (OCD-NET) and BDD (BDD-NET) in the Swedish public health system. Methods: Consecutive referrals to an outpatient psychiatric clinic providing ICBT, with a primary diagnosis of OCD or BDD, were included in the study. Four hundred and thirty-four participants started OCD-NET and 163 started BDD-NET. The primary outcome measures were the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Y-BOCS for BDD (BDD-YBOCS), respectively. Participants were assessed before treatment, weekly during treatment, and after treatment. The study used the RE-AIM implementation framework, and the elements of reach, effectiveness, adoption, and implementation for the evaluation. Results: Intention to treat analysis of the OCD-NET sample (n = 434) showed a significant decrease in OCD symptoms from pre-treatment to post-treatment (mean reduction = -8.77 [95 % CI -9.48 to -8.05] p < .001, d = 1.94 [95 % CI 1.75 to 2.13]). Forty-nine percent (95 % CI 43 % to 56 %) of the participants in OCD-NET were classified as treatment responders and 21 % (95 % CI 16 % to 27 %) were in remission. Participants in BDD-NET (n = 163) also showed a significant decrease in BDD symptoms from pre-post treatment (mean reduction = -11.37 [95 % CI -12.9 to -9.87] p < .001, d = 2.07 [95 % CI 1.74 to 2.40]) and 69 % (95 % CI 58 % to 79 %) of the participants were classified as treatment responders and 48 % (95 % CI 38 % to 58 %) were in full or partial remission. Eighty-seven percent of the participants in OCD-NET and 78 % in BDD-NET were treatment completers and participants in both treatment groups reported a high treatment satisfaction at post treatment (OCD-NET = 87 %, BDD-NET = 79 %). The most reported negative effects attributed to the treatments were transient experiences of unpleasant feelings (52 %) and anxiety (50 %). The implementation also influenced treatment delivery and dramatically decreased the mean number of patients waiting to receive face-to-face treatment at the clinic. Conclusions: Our results indicate that OCD-NET and BDD-NET are suitable treatments for implementation in a Swedish public health service.

Empirically Defining Treatment Response and Remission in Obsessive-Compulsive Disorder Using the Obsessive-Compulsive Inventory-Revised.

In clinical trials of obsessive-compulsive disorder (OCD), clinical outcomes are generally measured using lengthy clinician-administered interviews. However, in routine clinical practice, many clinicians lack the time to administer such instruments. This study evaluated cutoffs for treatment response and remission in OCD using the self-rated Obsessive-Compulsive Inventory-Revised (OCI-R). Data from 349 patients in three clinical trials of cognitive-behavioral therapy for OCD were pooled for analysis. The OCI-R was compared to gold-standard criteria for response and remission based on the clinician-administered Yale-Brown Obsessive Compulsive Scale and the Clinical Global Impression Scale. The results showed that a ≥40% reduction on the OCI-R was the optimal cutoff for treatment response, with a sensitivity of 0.72 and a specificity of 0.79. For remission status, the optimal cutoff was ≤8 points on the OCI-R, with a sensitivity of 0.57 and specificity of 0.83. Results from additional analyses using the 12-item version of the OCI were similar. These cutoffs provide a simple and time-efficient way to help determine treatment response and remission in OCD when the administration of clinician-administered instruments is unfeasible.

Facile preparation of a metal-phenolic network-based lymph node targeting nanovaccine for antitumor immunotherapy.

Cancer vaccines are being explored for enhanced cancer immunotherapy and prophylaxis. Some of their prevailing weaknesses, however, such as complicated preparation, poor biocompatibility, and failure to elicit strong cellular immune responses, have limited their further clinical applications. Here, we reported a multifunctional nanovaccine that was prepared in a quick and simple way. During the self-assembly of metal-phenolic networks (MPNs), the antigen ovalbumin (OVA) and immunoreactive chlorogenic acid (CHA) were simultaneously loaded. Owing to its dual pH and reduction sensitivities, the nanovaccine could deliver antigens into the cytoplasm of dendritic cells (DCs) and facilitate the cross-presentation of antigens. Moreover, the results of in vivo immunization assays demonstrated that the nanovaccine significantly excited the antigen presentation of DCs and provoked a robust cellular immune response with the restrained activation of regulatory T cells (Tregs), by targeting lymph nodes and executing the function of CHA. In vivo antitumor assays indicated that the nanovaccine with good biocompatibility afforded conspicuous cancer treatment and prevention effects. Overall, the nanovaccine presented in this study shows a promise for potentiating cancer immunotherapy by the lymph node-targeted delivery. STATEMENT OF SIGNIFICANCE: Cancer nanovaccines can be used for cancer immunotherapy. However, some existing shortcomings, such as cumbersome preparation, poor biocompatibility, and failure to elicit strong immune responses, limit the clinical application of cancer nanovaccines. This study developed a multifunctional nanovaccine that was readily prepared through the self-assembly of metal-phenolic networks. The nanovaccine with dual pH and reduction sensitivities could efficiently promote the antigen lysosome escape and cross-presentation. In vivo, it efficiently delivered antigen into lymph nodes and provoked strong cellular immune responses, and thus it showed significant cancer immunotherapy and prevention effect.

Broadband saturable absorption of indium tin oxide nanocrystals toward mid-infrared regime.

We experimentally demonstrate the ultrabroadband optical nonlinearity of indium tin oxide nanocrystals (ITO NCs) in the mid-infrared regime. Especially, the ITO NCs show considerable saturation absorption behavior with large modulation depth covering the spectral range from 2-µm to 10-µm wavelength. We also demonstrate the application of the optical nonlinearity to successfully modulate the erbium-doped fluoride fiber laser to deliver a nanosecond pulse with a signal-to-noise ratio over 43 dB at 2.8-µm wavelength. The results provide a promising platform for the development of ITO-based broadband and robust optoelectronic devices toward the deep mid-infrared spectral range.

Achievements and Perspectives on Fe-Based Shape Memory Alloys for Rehabilitation of Reinforced Concrete Bridges: An Overview.

Reinforced concrete (RC) bridges often face great demands of strengthening or repair during their service life. Fe-based shape memory alloys (Fe-SMAs) as a kind of low-cost smart materials have great potential to enhance civil engineering structures. The stable shape memory effect of Fe-SMAs is generated by, taking Fe-Mn-Si alloys as an example, the martensite transformation of fcc(γ) → hcp(ε) and its reverse transformation which produces considerable recovery stress (400~500 MPa) that can be used as prestress for reinforcement of RC bridges. In this work, the mechanism, techniques, and applications of Fe-SMAs in the reinforcement of RC beams in the past two decades are classified and introduced in detail. Finally, some new perspectives on Fe-SMAs application in civil engineering and their expected evolution are proposed. This paper offers an effective active rehabilitation alternative for the traditional passive strengthening method of RC bridges.

A Simple Doping Process Achieved by Modifying the Passivation Layer for Self-Aligned Top-Gate In-Ga-Zn-O Thin-Film Transistors at 200 °C.

In this paper, a facile modifying technique of source/drain regions conductivity was proposed for self-aligned top-gate In-Ga-Zn-O (IGZO) thin-film transistors (TFTs) by controlling the process parameter of the passivation layer at relatively low temperatures. The sheet resistance of the source and drain regions of IGZO was approximately 365 Ω/□, and there was no significant change within a month. The device parameters of mobility, threshold voltage, subthreshold swing, and current switching ratio of the fabricated device were 15.15 cm2V-1s-1, 0.09 V, 0.15 V/dec, and higher than 109, respectively. The threshold voltage drift under negative bias illumination stress was -0.34 V. In addition, a lower channel width-normalized contact resistance of 9.86 Ω·cm was obtained.

Visible optical nonlinearity of vanadium dioxide dispersions.

Vanadium dioxide (VO2), a correlated oxide compound, is one of the functional materials extensively studied in solid state physics due to its attractive physical properties. However, the nonlinear optical response of VO2 and related all-optical applications have been paid less attention. Here, the nonlinear refractive index (n 2) and third-order nonlinear susceptibility (χ (3)) of VO2 dispersions have been acquired to be 3.06 × 10-6 cm2 W-1 and 1.68 × 10-4 esu at a wavelength of 671 nm, and 5.17 × 10-6 cm2 W-1 and 2.83 × 10-4 esu at a wavelength of 532 nm via the spatial self-phase modulation (SSPM) and spatial cross-phase modulation (SXPM) effects in the visible regime, respectively. Based on the excellent nonlinear optical properties of VO2 dispersions, the proof-of-principle functions such as optical logic or-gates, all-optical switches, and inter-channel information transfer are implemented in the visible wavelength. The experimental results on the response time of VO2 to light indicate that the formation of diffraction rings is mainly an electronically coherent third-order nonlinear optical process. The experimental results show that the VO2 dispersions exhibit an excellent nonlinear optical response and may lay the foundation for the application of VO2-based all-optical devices.

Inhibiting 3ßHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer.

Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens. In this study, mass-spectrometry-based screening of clinical specimens and a retrospective analysis on the clinical data of prostate cancer patients indicate the potential oncogenic effects of progesterone in patients. High doses of progesterone activate canonical and non-canonical androgen receptor (AR) target genes. Physiological levels of progesterone facilitate cell proliferation via GATA2. Inhibitors of 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) has been discovered and shown to suppress the generation of progesterone, eliminating its transient and accumulating oncogenic effects. An increase in progesterone is associated with poor clinical outcomes in patients and may be used as a predictive biomarker. Overall, we demonstrate that progesterone acts as an oncogenic hormone in prostate cancer, and strategies to eliminate its oncogenic effects may benefit prostate cancer patients.

CO2-Low Interfacial Tension Viscoelastic Fluid Synergistic Flooding in Tight Reservoirs.

Tight oil reservoirs have poor physical properties, insufficient formation energy, and low natural productivity. CO2 flooding is an important technical mean that enhances the oil recovery of dense reservoirs and achieves effective CO2 sequestration, but strong heterogeneity of the tight oil reservoir usually results in gas channeling and poor enhanced oil recovery effect. The existing methods to prevent gas channeling are mainly to use the small-molecule amine system and the polymer gel system to plug fracture and high permeability channels. The small-molecular amine system has low flash points and pollutes the environment and the polymer gel has poor injectivity and great damage to the formation, which limit their large-scale application. Therefore, a new viewpoint of CO2-low interfacial tension viscoelastic fluid synergistic flooding for enhanced oil recovery in a tight oil reservoir was made. The performance of low interfacial tension viscoelastic fluid (GOBT) was studied. The injectivity and oil displacement effect of CO2-GOBT synergistic flooding were evaluated, and the mechanism of CO2-GOBT synergistic flooding was discussed. The experimental results showed that 0.4% GOBT is a low interfacial tension viscoelastic fluid, which has strong adaptability to the salinity water of tight oil reservoirs (6788-80,000 mg/L), good viscosity stability at different pHs, excellent capacity to emulsify crude oil, and the ability to improve reservoir water wettability. CO2 alternating 0.4% GOBT flooding has good injection ability in cores (K a = 0.249 mD), and injecting 0.4% GOBT can effectively increase the injection pressure of subsequent CO2 flooding. CO2 alternating 0.4% GOBT flooding can effectively improve water flooding recovery in tight sandstone reservoirs, which is better than CO2 flooding and 0.4% GOBT flooding in both homogeneous and heterogeneous conditions. The mechanisms of CO2 alternating 0.4% GOBT flooding to enhance the oil recovery include that GOBT and CO2 foam block high permeability layers, shunt and sweep low permeability layers, and GOBT emulsify and wash oil. CO2 partially dissolving in GOBT synergistically enhances the core water wettability, which improves GOBT injectability, emulsification, and stripping ability to residual oil.

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia.

HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported S. aureus vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model. Results showed that HI-mediated protection was altered in response to different adjuvants. Using antisera from immunized mice, we identified seven B-cell immunodominant epitopes on Hla and IsdB, including 6 novel epitopes (Hla1-18, Hla84-101, Hla186-203, IsdB342-359, IsdB366-383, and IsdB384-401). The immunodominance of B-cell epitopes, total IgG titers and the levels of IFN-γ and IL-17A from mice immunized with HI plus different adjuvants were different from each other, which may explain the difference in protective immunity observed in each immunized group. Thus, our results indicate that adjuvants largely affected the immunodominance of epitopes and the protective efficacy of HI, which may guide further adjuvant screening for vaccine development and optimization.

Empirically Defining Treatment Response and Remission in Body Dysmorphic Disorder Using a Short Self-Report Instrument.

Determining response or remission status in body dysmorphic disorder (BDD) usually requires a lengthy interview with a trained clinician. This study sought to establish empirically derived cutoffs to define treatment response and remission in BDD using a brief self-report instrument, the Appearance Anxiety Inventory (AAI). Results from three clinical trials of BDD were pooled to create a sample of 123 individuals who had received cognitive-behavioral therapy for BDD, delivered via the Internet. The AAI was compared to gold-standard criteria for response and remission in BDD, based on the clinician-administered Yale-Brown Obsessive Compulsive Scale, modified for BDD (BDD-YBOCS), and evaluated using signal detection analysis. The results showed that a ≥ 40% reduction on the AAI best corresponded to treatment response, with a sensitivity of 0.71 and a specificity of 0.84. A score ≤ 13 at posttreatment was the optimal cutoff in determining full or partial remission from BDD, with a sensitivity of 0.75 and a specificity of 0.88. These findings provide benchmarks for using the AAI in BDD treatment evaluation when resource-intensive measures administered by clinicians are not feasible.

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Pollen-Shaped Hierarchical Structure for Pressure Sensors with High Sensitivity in an Ultrabroad Linear Response Range.

High sensitivity and linear response over a wide sensing range are important in flexible pressure sensors for their practical applications in biomimetic electronics and human-machine interactions. Previous studies regarding flexible pressure sensors have primarily focused on their high sensitivity, whereas they generally exhibit a narrow linear sensing range. In this article, a hierarchical structure with conical secondary features is reported, and its role in enhancing the linear sensing range of piezoresistive pressure sensors is demonstrated. We find that the conical secondary features on the hierarchical structure significantly improve the linear relationship between the contact area and applied force over a broad range. This advantage endows the sensor with a wide linear sensing range. To obtain this type of hierarchical structure, pollen grains of wild chrysanthemum are exploited as templates, and the prepared sensor presents a high sensitivity of 3.5 kPa-1 over an ultrawide response range of 0-218 kPa with good linearity via a coefficient of determination (R2) of 0.997. Furthermore, owing to the simple and scalable process, a sensor array with high density is fabricated to map the spatial pressure distribution and simulate an electronic skin to detect Braille characteristics.

Transparent Nanostructured BiVO4 Double Films with Blue Light Shielding Capabilities to Prevent Damage to ARPE-19 Cells.

The hazards posed by blue light to human eyes are attracting significant attention owing to increasing exposure to electronic devices as well as artificial illumination. Therefore, in this study, nanostructured BiVO4 (BVO) double films were developed using an economical and environmentally friendly sol-gel spin-coating method; the films exhibited excellent blue light shielding capabilities. They could block 65.25% of the blue light in the 415-455 nm wavelength range while simultaneously maintaining an average transmittance greater than 85% in the 500-800 nm wavelength range. Moreover, the damp heat test (85 °C, 85% relative humidity) showed the excellent stability of the BVO filters as their transmittances remained unchanged for 15 days. Importantly, cell experiments were performed to further confirm the protective effects of the BVO filters against the hazards posed by blue light to ARPE-19 cells (human retinal pigment epithelium cell line). Furthermore, the blue light weighted radiance LB decreased by 34.32%, and the color rendering index showed negligible differences after applying an upscaled BVO filter to a phone screen. These cost-efficient, ecofriendly, highly reliable, and large-area nanostructured BVO films with high blue light shielding efficiency have potential applications in various areas.