The Association Between Antidepressant Use and Drug-Induced Liver Injury: A Nationwide, Population-Based Case-Control Study in Taiwan.

BACKGROUND AND OBJECTIVE: The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. METHODS: The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. RESULTS: The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95% CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29). CONCLUSION: SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

The roles of bacteria and viruses in COPD-Bronchiectasis association: A prospective cohort study.

BACKGROUND: Exacerbations are implicated in bronchiectasis and COPD, which frequently co-exist [COPD-Bronchiectasis association (CBA)]. We aimed to determine the bacterial and viral spectrum at stable-state and exacerbation onset of CBA, and their association between pathogen detection and with exacerbations of CBA as compared with bronchiectasis. METHODS: We prospectively collected spontaneous sputum from adults with CBA, bronchiectasis with (BO) and without airflow obstruction (BNO) for bacterial culture and viral detection at stable-state and exacerbations. RESULTS: We enrolled 76 patients with CBA, 58 with BO, and 138 with BNO (711 stable and 207 exacerbation visits). Bacterial detection rate increased from BNO, CBA to BO at steady-state (P=0.02), but not at AE onset (P=0.91). No significant differences in viral detection rate were found among BNO, CBA and BO. Compared with steady-state, viral isolations occurred more frequently at exacerbation in BNO (15.8% vs 32.1%, P=0.001) and CBA (19.5% vs 30.6%, P=0.036) only. In CBA, isolation of viruses, human metapneumovirus and bacteria plus viruses was associated with exacerbation. Repeated detection of Pseudomonas aeruginosa correlated with higher modified Reiff score (P=0.032) in CBA but not in BO (P=0.178). Repeated detection of Pseudomonas aeruginosa yielded a shorter time to the first exacerbation in CBA [median: 4.3 vs 11.1 months, P=0.006] but not in BO (median: 8.4 vs 7.6 months, P=0.47). CONCLUSIONS: Patients with CBA have greater disease severity than those with BNO. While isolation of viruses is associated with CBA exacerbations, repeated detection of Pseudomonas aeruginosa confers greater impact of future exacerbations on CBA than on BO.

Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes.

Uveal melanoma (UM) is a rare but aggressive malignant ocular tumor with a high metastatic potential and limited therapeutic options, currently lacking accurate prognostic predictors and effective individualized treatment strategies. Public databases were utilized to analyze the prognostic relevance of programmed cell death-related genes (PCDRGs) in UM transcriptomes and survival data. Consensus clustering and Lasso Cox regression analysis were performed for molecular subtyping and risk feature construction. The PCDRG-derived index (PCDI) was evaluated for its association with clinicopathological features, gene expression, drug sensitivity, and immune infiltration. A total of 369 prognostic PCDRGs were identified, which could cluster UM into 2 molecular subtypes with significant differences in prognosis and clinicopathological characteristics. Furthermore, a risk feature PCDI composed of 11 PCDRGs was constructed, capable of indicating prognosis in UM patients. Additionally, PCDI exhibited correlations with the sensitivity to 25 drugs and the infiltration of various immune cells. Enrichment analysis revealed that PCDI was associated with immune regulation-related biological processes and pathways. Finally, a nomogram for prognostic assessment of UM patients was developed based on PCDI and gender, demonstrating excellent performance. This study elucidated the potential value of PCDRGs in prognostic assessment for UM and developed a corresponding risk feature. However, further basic and clinical studies are warranted to validate the functions and mechanisms of PCDRGs in UM.

Temporal-Focusing Multiphoton Excitation Single-Molecule Localization Microscopy Using Spontaneously Blinking Fluorophores.

Single-molecule localization microscopy (SMLM) based on temporal-focusing multiphoton excitation (TFMPE) and single-wavelength excitation is used to visualize the three-dimensional (3D) distribution of spontaneously blinking fluorophore-labeled subcellular structures in a thick specimen with a nanoscale-level spatial resolution. To eliminate the photobleaching effect of unlocalized molecules in out-of-focus regions for improving the utilization rate of the photon budget in 3D SMLM imaging, SMLM with single-wavelength TFMPE achieves wide-field and axially confined two-photon excitation (TPE) of spontaneously blinking fluorophores. TPE spectral measurement of blinking fluorophores is then conducted through TFMPE imaging at a tunable excitation wavelength, yielding the optimal TPE wavelength for increasing the number of detected photons from a single blinking event during SMLM. Subsequently, the TPE fluorescence of blinking fluorophores is recorded to obtain a two-dimensional TFMPE-SMLM image of the microtubules in cancer cells with a localization precision of 18±6 nm and an overall imaging resolution of approximately 51 nm, which is estimated based on the contribution of Nyquist resolution and localization precision. Combined with astigmatic imaging, the system is capable of 3D TFMPE-SMLM imaging of brain tissue section of a 5XFAD transgenic mouse with the pathological features of Alzheimer's disease, revealing the distribution of neurotoxic amyloid-beta peptide deposits.

TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis.

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.

Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

Paenibacillus baimaensis sp. nov., a bacterium isolated from mountain soil in the habitat of Rhinopithecus bieti.

A novel Gram-positive strain WQ 127069T that was isolated from the soil of Baima Snow Mountain, a habitat of highly endangered Yunnan snub-nosed monkeys (Rhinopithecus bieti), was subjected to a polyphasic taxonomic study. Phylogenetic analysis based on the 16S rRNA gene sequences showed that the isolate belongs to the genus Paenibacillus, showing 98.4 and 96.08 % sequence similarity to the type strains Paenibacillus periandrae PM10T and Paenibacillus foliorum LMG 31456T, respectively. The G+C content of the genomic DNA of strain WQ127069T was 45.6 mol%. The predominant isoprenoid quinone was MK-7, and meso-diaminopimelic acid was present in peptidoglycan. The major cellular fatty acids were antiiso-C15 : 0, iso-C15 : 0 and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylmonomethylethanolamine. The whole genome average nucleotide identity and digital DNA-DNA hybridization values between strain WQ 127069T and strain PM10T were 93.2 and 52.5 %, respectively. Growth occurred at 5-40 °C (optimally at 20-35 °C), pH 6-8 (optimally at pH7.0) and with 0.5-2 % (w/v) NaCl (optimally at 0.5 %). On the basis of the taxonomic evidence, a novel species, Paenibacillus baimaensis sp. nov., is proposed. The type strain is WQ 127069T (=KCTC 43480T=CCTCC AB 2022381T).

Cytosolic mtDNA-cGAS-STING axis contributes to sepsis-induced acute kidney injury via activating the NLRP3 inflammasome.

BACKGROUND: NLRP3 inflammasome activation is significantly associated with sepsis-induced acute kidney injury (S-AKI). Cytosolic DNA derived from damaged mitochondria has been reported to activate NLRP3 inflammasome via upregulating the cyclic GMP-AMP synthase (cGAS)-the stimulator of interferon genes (STING) axis in nucleus pulposus cell and cardiomyocytes. However, the regulatory effect of mitochondria DNA (mtDNA)-cGAS-STING axis on the NLRP3 inflammasome in S-AKI remains unclear. METHODS: In the current study, we established an in vivo model of S-AKI by intraperitoneally injecting male C57BL/6 J mice with lipopolysaccharide (LPS). Next, selective cGAS inhibitor RU.521, and STING agonist DMXAA were intraperitoneally injected in the mice; then, blood urea nitrogen (BUN), serum creatinine (CRE), urinary kidney injury molecular-1 (KIM-1), pathological changes, and infiltrated neutrophils were detected to assess kidney injury. We also performed western blot and immunofluorescence assays to evaluate STING, cGAS, TBK-1, p-TBK-1, IRF3, p-IRF3, NF-kB, p-NF-kB, NLRP3, cleaved caspase-1, caspase-1, GSDMD-N, and GSDMD expression levels in kidney tissues. IL-18 and IL-1ß in renal tissue were identified by ELISA. In vitro, we treated HK-2 cells with LPS to establish a cell model of S-AKI. Furthermore, ethidium bromide (EtBr) was administered to deplete mitochondria DNA (mtDNA). LPS-induced cytotoxicity was evaluated by LDH release assay. Protein expression of cGAS, STING, and NLRP3 in was quantified by western blot. Cytosolic mtDNA was detected by immunofluorescence and q-PCR. Released IL-1ß and IL-18 in HK-2 supernatants were detected by ELISA. RESULTS: LPS injection induced S-AKI in mice, as evidenced by neutrophil infiltration, tubular vacuolation, and increased levels of serum creatinine (CRE), blood urea nitrogen (BUN), and urinary KIM-1. In addition, LPS activated the cGAS-STING axis and NLRP3 inflammasome in vivo, illustrated by increased phosphorylation levels of TBK-1, IRF3, and NF-kB protein, increased ratio of cleaved caspase-1 to caspase-1 and GSDMD-N to GSDMD, and increased IL-1ß and IL-18 levels. Moreover, the cGAS inhibitor RU.521 effectively attenuated NLRP3 inflammasome and S-AKI; however, these effects were abolished by treatment with the STING agonist DMXAA. Furthermore, cytosolic release of mtDNA and activation of the cGAS-STING-NLRP3 axis were observed in LPS-treated HK-2 cells. Inhibiting mtDNA replication by Ethidium Bromide (EtBr) treatment reduced cytosolic mtDNA accumulation and downregulated the cGAS-STING-NLRP3 axis, ameliorating the cytotoxicity induced by LPS. CONCLUSION: This study demonstrated that the cGAS-STING axis was triggered by cytosolic mtDNA and participated in the development of S-AKI by activating NLRP3 inflammasome. Reducing cytosolic mtDNA accumulation or inhibiting the cGAS-STING axis may be potential therapeutic targets for S-AKI.

Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

BACKGROUND: Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. OBJECTIVE: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. METHODS: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. RESULTS: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). CONCLUSION: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

Feasibility and Safety of 5G-Based Telerobotic Abdominal Ultrasonography.

OBJECTIVE: Telemedicine can offer services to remote patients regardless of the distance. Fifth-generation (5G) mobile networks may make telemedicine practical because of their low latency. This study aimed to evaluate the feasibility and safety of a novel 5G robot-assisted remote abdominal ultrasound (AUS) telemedicine technology in clinical applications in distant locations. METHODS: We performed 5G-based telerobotic AUS in patients who were located more than 100 km away from the physicians. RESULTS: The telerobotic AUS had a longer examination time than the conditional bedside AUS; however, the complete examination rate was not inferior. None of the volunteers experienced discomfort during the examination and the examination time was acceptable for all. CONCLUSION: Our findings confirm the feasibility and safety of 5G-based telerobotic AUS in clinical practice.

A pilot study of non-invasive diagnostic tools to detect Helicobacter pylori infection and peptic ulcer disease.

Helicobacter pylori (H. pylori) infection can lead to various digestive system diseases, making accurate diagnosis crucial. However, not all available tests are equally non-invasive and sensitive. This study aimed to compare the efficacy of non-invasive and invasive diagnostic tools for H. pylori infection and assess their correlation with esophagogastroduodenoscopic (EGD) findings. The study utilized the Campylobacter-Like Organism (CLO) test, serum anti-HP IgG blood test, and C-13-urea breath test (UBT) to diagnose H. pylori infection. A total of 100 patients with peptic ulcer symptoms, including 45 males and 55 females, were recruited for the study. Symptomatic patients between the ages of 20-70, eligible for EGD examination, were enrolled. Each diagnostic test and any combination of two positive tests were considered the reference standard and compared against the other diagnostic methods. Additionally, the relationship between these diagnostic tests and EGD findings was evaluated. Among the participants, 74.0% were diagnosed with peptic ulcer disease through EGD. The UBT demonstrated the highest Youden's index, ranging from 58 to 100%, against all the non-invasive tests. The IgG blood test displayed the highest sensitivity at 100%, with a specificity of 60-70%. On the other hand, the CLO test exhibited the highest specificity at 100% and a sensitivity of 50-85%. Furthermore, only the CLO test showed a significant association with esophageal ulcers (p-value = 0.01). The IgG blood test holds promise as a primary screening tool due to its exceptional sensitivity. While the UBT is relatively expensive, its non-invasive nature and high sensitivity and specificity make it a potential standalone diagnostic test for H. pylori infection. Moreover, the noteworthy negative correlation between the CLO test and esophageal ulcers provides evidence of the differing effects of H. pylori infection on antral-predominant and corpus-predominant gastritis.

Differential airway resistome and its correlations with clinical characteristics in Haemophilus- or Pseudomonas-predominant microbial subtypes of bronchiectasis.

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.

A Fluorescent Vector of Carbon Dot to Deliver Rab13 and Rab14 Plasmids for Promoting Neurite Outgrowth.

The complex processes of neuron differentiation and neuron repair are critical for treating nervous system injuries and neurodegenerative diseases. Neurite outgrowth plays a crucial role in these processes by enabling the formation of connections between neurons and the generation of neuroplasticity to restore the function of the nervous system. In this study, we fabricated functionalized carbon dots (CDs) with distinctive photoluminescence and low cytotoxicity for use as fluorescence imaging probes and nanocarriers to deliver plasmid DNAs to neurons effectively for inducing neurite outgrowth. CDs were prepared through a reflux process in nitric acid solution, and their surface was then modified using polyethylenimine (PEI) to obtain positively charged CDs for increasing the absorption of plasmid DNAs and the efficiency of cell uptake. Experimental results indicated that the fabricated CDs maintained a low cytotoxicity and exhibited a high neuron uptake of up to 97%. An improvement in the plasmid DNA ingestion of neurons resulted in enhanced expression of Rab13-Q67L and Rab14 proteins, which considerably promoted neurite sprouting and elongation. After the fabricated PEI-modified CDs were used to deliver the Rab13-Q67L and Rab14 plasmids, more than 56% of the neurons had a neurite length that was greater than twice the size of their soma. Thus, DNA delivery through functionalized CDs has a high potential for use in gene therapy for neuronal injuries and diseases.

Soft and stretchable organic bioelectronics for continuous intraoperative neurophysiological monitoring during microsurgery.

In microneurosurgery, it is crucial to maintain the structural and functional integrity of the nerve through continuous intraoperative identification of neural anatomy. To this end, here we report the development of a translatable system leveraging soft and stretchable organic-electronic materials for continuous intraoperative neurophysiological monitoring. The system uses conducting polymer electrodes with low impedance and low modulus to record near-field action potentials continuously during microsurgeries, offers higher signal-to-noise ratios and reduced invasiveness when compared with handheld clinical probes for intraoperative neurophysiological monitoring and can be multiplexed, allowing for the precise localization of the target nerve in the absence of anatomical landmarks. Compared with commercial metal electrodes, the neurophysiological monitoring system allowed for enhanced post-operative prognoses after tumour-resection surgeries in rats. Continuous recording of near-field action potentials during microsurgeries may allow for the precise identification of neural anatomy through the entire procedure.

Resveratrol­mediated activation of SIRT1 inhibits the PERK­eIF2α­ATF4 pathway and mitigates bupivacaine­induced neurotoxicity in PC12 cells.

Endoplasmic reticulum (ER) stress and apoptosis play significant roles in the development of neurotoxicity caused by bupivacaine (BUP). By activating sirtuin 1 (SIRT1), resveratrol (RSV) can regulate various cellular processes associated with anti-oxidative stress, anti-apoptosis and anti-inflammatory responses, thereby exerting neuroprotective effects. However, it remains unknown whether the activation of SIRT1 by RSV is able to attenuate BUP-induced ER stress and apoptosis. Therefore, the present study aimed to explore the effect of RSV on BUP-induced cytotoxicity in PC12 cells and the underlying mechanism. Cell Counting Kit-8 assays, flow cytometry and inverted phase-contrast microscopy were used to assess the viability, apoptosis rate and morphological changes of the cells, respectively. Western blotting and immunofluorescence staining were used to analyze the levels of SIRT1, the apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3, the ER stress-related proteins glucose-regulated protein 78, caspase-12 and CHOP, and the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 α (eIF2α)-activating transcription factor 4 (ATF4) pathway-associated proteins phosphorylated (p)-PERK, PERK, p-eIF2α, eIF2α and ATF4. The results revealed that BUP induced cell apoptosis and decreased cell viability, accompanied by the downregulation of SIRT1. However, RSV restored SIRT1 protein expression, downregulated the expression of the pro-apoptotic protein Bax, upregulated the expression of the anti-apoptotic protein Bcl-2, decreased the apoptosis rate of the cells and increased cell viability. Furthermore, the anti-apoptotic effects exhibited by RSV were associated with inhibition of the PERK-eIF2α-ATF4 pathway of ER stress. However, the protective effect of RSV was significantly mitigated by the SIRT1 inhibitor EX527. These results indicate that the activation of SIRT1 by RSV alleviates BUP-induced PC12 cell ER stress and apoptosis via regulation of the PERK-eIF2α-ATF4 pathway. These findings offer insights into the molecular mechanism underlying BUP-induced apoptosis and suggest the potential of RSV as a therapeutic agent against the neurotoxicity caused by BUP.

Colorful low-emissivity paints for space heating and cooling energy savings.

Space heating and cooling consume ~13% of global energy every year. The development of advanced materials that promote energy savings in heating and cooling is gaining increasing attention. To thermally isolate the space of concern and minimize the heat exchange with the outside environment has been recognized as one effective solution. To this end, here, we develop a universal category of colorful low-emissivity paints to form bilayer coatings consisting of an infrared (IR)-reflective bottom layer and an IR-transparent top layer in colors. The colorful visual appearance ensures the aesthetical effect comparable to conventional paints. High mid-infrared reflectance (up to ~80%) is achieved, which is more than 10 times as conventional paints in the same colors, efficiently reducing both heat gain and loss from/to the outside environment. The high near-IR reflectance also benefits reducing solar heat gain in hot days. The advantageous features of these paints strike a balance between energy savings and penalties for heating and cooling throughout the year, providing a comprehensive year-round energy-saving solution adaptable to a wide variety of climatic zones. Taking a typical midrise apartment building as an example, the application of our colorful low-emissivity paints can realize positive heating, ventilation, and air conditioning energy saving, up to 27.24 MJ/m2/y (corresponding to the 7.4% saving ratio). Moreover, the versatility of the paint, along with its applicability to diverse surfaces of various shapes and materials, makes the paints extensively useful in a range of scenarios, including building envelopes, transportation, and storage.

Investigation of Sm Addition on Microstructural and Optical Properties of CoFe Thin Films.

CoFe-based alloys and rare earth (RE) elements are among the most studied materials in applying magnetic devices to improve soft magnetic characteristics. A series of Co40Fe40Sm20 films are deposited on a glass substrate via the sputtering technique, followed by an annealing process to investigate their effect on microstructural and optical properties of Co40Fe40Sm20 films. In this study, the increase in the thickness of Co40Fe40Sm20 films and annealing temperatures resulted in a smoother surface morphology. The 40 nm Co40Fe40Sm20 films annealed 300 °C are expected to have good wear resistance and adhesive properties due to their high values of H/E ratio and surface energy. Optical transparency also increased due to the smoother surface of the Co40Fe40Sm20 films.