Deep Learning with Pretrained Framework Unleashes the Power of Satellite-Based Global Fine-Mode Aerosol Retrieval.

Fine-mode aerosol optical depth (fAOD) is a vital proxy for the concentration of anthropogenic aerosols in the atmosphere. Currently, the limited data length and high uncertainty of the satellite-based data diminish the applicability of fAOD for climate research. Here, we propose a novel pretrained deep learning framework that can extract information underlying each satellite pixel and use it to create new latent features that can be employed for improving retrieval accuracy in regions without in situ data. With the proposed model, we developed a new global fAOD (at 0.5 µm) data from 2001 to 2020, resulting in a 10% improvement in the overall correlation coefficient (R) during site-based independent validation and a 15% enhancement in non-AERONET site areas validation. Over the past two decades, there has been a noticeable downward trend in global fAOD (-1.39 × 10-3/year). Compared to the general deep-learning model, our method reduces the global trend's previously overestimated magnitude by 7% per year. China has experienced the most significant decline (-5.07 × 10-3/year), which is 3 times greater than the global trend. Conversely, India has shown a significant increase (7.86 × 10-4/year). This study bridges the gap between sparse in situ observations and abundant satellite measurements, thereby improving predictive models for global patterns of fAOD and other climate factors.

Fusible and Radiopaque Microspheres for Embolization.

In this work, fusible microspheres loaded with radiopaque agents as an embolic agent for transcatheter arterial embolization (TAE) are developed. A poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) multi-block copolymer basing polyurethane (PCEU) is synthesized and fabricated into blank microspheres (BMs). The microspheres are elastic in compression test. A clinical contrast agent lipiodol is encapsulated in the microspheres to receive fusible radiopaque microspheres (FRMs). The sizes of FRMs are uniform and range from 142.2 to 343.1 µm. The encapsulated lipiodol acts as the plasticizer to reduce the melting temperature point (Tm) of PECU microspheres, thus, leading to the fusion of microspheres to exhibit efficient embolization in vivo. The performance of FRMs is carried out on a rabbit ear embolization model. Serious ischemic necrosis is observed and the radiopacity of FRMs sustains much longer time than that of commercial contrast agent Loversol in vivo. The fusible and radiopaque microsphere is promising to be developed as an exciting embolic agent.

Robotic flytrap with an ultra-sensitive 'trichome' and fast-response 'lobes'.

Nature abounds with examples of ultra-sensitive perception and agile body transformation for highly efficient predation as well as extraordinary adaptation to complex environments. Flytraps, as a representative example, could effectively detect the most minute physical stimulation of insects and respond instantly, inspiring numerous robotic designs and applications. However, current robotic flytraps face challenges in reproducing the ultra-sensitive insect-touch perception. In addition, fast and fully-covered capture of live insects with robotic flytraps remains elusive. Here we report a novel design of a robotic flytrap with an ultra-sensitive 'trichome' and bistable fast-response 'lobes'. Our results show that the 'trichome' of the proposed robotic flytrap could detect and respond to both the external stimulation of 0.45 mN and a tiny touch of a flying bee with a weight of 0.12 g. Besides, once the 'trichome' is triggered, the bistable 'lobes' could instantly close themselves in 0.2 s to form a fully-covered cage to trap the bees, and reopen to set them free after the tests. We introduce the design, modeling, optimization, and verification of the robotic flytrap, and envision broader applications of this technology in ultra-sensitive perception, fast-response grasping, and biomedical engineering studies.

Constructing nitrogen-doped graphene quantum dots embedded in CNT supported layered (Ni0.5Co0.5)3V2O8 self-supporting film for high-performance supercapacitor.

To improve the electrochemical performance of positive electrode materials, constructing graded nanostructures is a worthwhile approach. This study successfully synthesized nitrogen-doped graphene quantum dots (NGQD) modified (Ni0.5Co0.5)3V2O8 on a carbon nanotube (CNT) substrate to construct self-supporting electrodes for high-performance supercapacitors. The (Ni0.5Co0.5)3V2O8 nanosheets were successfully wrapped onto the CNT surface through a solution impregnation process, which increased the specific surface area and interlayer spacing of the material. Furthermore, the electrochemical properties of the electrode material underwent significant enhancement due to the synergistic interplay between metal ions and the numerous redox centers. The embedding of the NGQD enriched the materials with active sites and further improved its specific capacity without compromising the structure intergrity of the layer configuration. Using CNT as the substrate ensured the self-supporting nature of the electrode. Consequently, the (Ni0.5Co0.5)3V2O8/NGQD@CNT composite exhibits an ultra-high specific capacitance of 3018.2 F g-1 at 1 A g-1 and 2332 F g-1 at 10 A g-1. The asymmetric supercapacitor constructed with (Ni0.5Co0.5)3V2O8/NGQD@CNT and activated carbon (AC) presented an impressive energy density of 160.2 Wh kg-1 at a power density of 800 W kg-1. After 8000 charge-discharge cycles, the capacity retention rate was 78.5 %, with a Coulo mbic efficiency consistently above 98 %.

Methionine Improves Boar Sperm Quality by Promoting Mitochondrial Translation during Liquid Storage.

Boar sperm quality serves as an important indicator of reproductive efficiency, playing a direct role in enhancing the output of livestock production. It has been demonstrated that mitochondrial protein translation is present in sperm and plays a crucial role in regulating sperm motility, capacitation and in vitro fertilization rate. The present study aimed to determine whether methionine supplementation enhances mitochondrial translation in boar sperm, thereby improving sperm quality. The results showed a significant elevation in the abundance of mitochondrial methionyl-tRNA formyltransferase (MTFMT), a crucial enzyme for mitochondrial protein translation, and mitochondrial DNA-encoded cytochrome c oxidase subunit 1 (COX1) in boar sperm exhibiting high motility. Both amino acids and methionine supplementation significantly enhanced boar sperm motility during storage. Moreover, methionine supplementation mitigates the loss of acrosomal integrity, enhances the expression of COX1, and boosts mitochondrial activity. Furthermore, the positive impact of methionine was negated in the presence of the mitochondrial translation inhibitor chloramphenicol. Together, these findings suggest that boar sperm may utilize methionine as a protein translation substrate to enhance sperm motility by stimulating mitochondrial protein translation. The supplementation of methionine may enhance the quality of boar sperm, thereby providing guidance for the optimization of diluent formulations for liquid storage and the identification of physiological regulators that regulate sperm motility.

Engineering Water-Lotus-like Iridium-Cobalt Carbonate Hydroxides on Plasma-Treated Carbon Fibers for Enhanced Electrocatalytic Oxygen Evolution.

The sluggish kinetics of the oxygen evolution reaction (OER) in alkaline water electrolysis remains a significant challenge for developing high-efficiency electrocatalytic systems. In this study, we present a three-dimensional, micrometer-sized iridium oxide (IrO2)-decorated cobalt carbonate hydroxide (IrO2-P-CoCH) electrocatalyst, which is engineered in situ on a carbon cloth (CC) substrate pretreated with atmospheric-pressure dielectric barrier discharge (DBD) plasma (PCC). The electrocatalyst features petal-like structures composed of nanosized rods, providing abundant reactive areas and sites, including the oxygen vacancy caused by the air-DBD plasma. As a result, the IrO2-P-CoCH/PCC electrocatalyst demonstrates an outstanding OER performance, with overpotentials of only 190 and 300 mV required to achieve current densities of 10 mA cm-2 (j10) and 300 mA cm-2 (j300), respectively, along with a low Tafel slope of 48.1 mV dec-1 in 1.0 M KOH. Remarkably, benefiting from rich active sites exposed on the IrO2-P-CoCH (Ir) heterostructure, the synergistic effect between IrO2 and CoCH enhances the charge delivery rates, and the IrO2-P-CoCH/PCC exhibits a superior electrocatalytic activity at a high current density (300 mV/j300) compared to the commercial benchmarked RuO2/PCC (470 mV/j300). Furthermore, the IrO2-P-CoCH/PCC electrocatalyst shows exceptional OER stability, with a mere 1.3% decrease with a current density of j10 for 100 h testing, surpassing most OER catalysts based on CC substrates. This work introduces a novel approach for designing high-performance OER electrocatalysts on flexible electrode substrates.

Highly efficient synthesis of enantioenriched vicinal halohydrins via Ir-catalyzed asymmetric hydrogenation using dynamic kinetic resolution.

A novel synthetic route was developed for the construction of chiral cis-vicinal halohydrins derivatives through Ir/f-phamidol-catalysed asymmetric hydrogenation of corresponding α-halogenated ketones with high yields (up to 99% yield), excellent diastereoselectivities (>20 : 1 dr), enantioselectivities (up to 99% ee), and high substrate catalyst ratio (S/C = 1000).

Rapid determination of toxic and essential metal binding proteins in biological samples by size exclusion chromatography-inductively coupled plasma tandem mass spectrometry.

Metalloproteins binding with trace elements play a crucial role in biological processes and on the contrary, those binding with exogenous heavy metals have adverse effects. However, the methods for rapid, high sensitivity and simultaneous analysis of these metalloproteins are still lacking. In this study, a fast method for simultaneously determination of both essential and toxic metal-containing proteins was developed by coupling size exclusion chromatography (SEC) with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). After optimization of the separation and detection conditions, seven metalloproteins with different molecular weight (from 16.0 to 443.0 kDa) were successfully separated within 10 min and the proteins containing iron (Fe), copper (Cu), zinc (Zn), iodine (I) and lead (Pb) elements could be simultaneously detected with the use of oxygen as the collision gas in ICP-MS/MS. Accordingly, the linear relationship between log molecular weight and retention time was established to estimate the molecular weight of unknown proteins. Thus, the trace metal and toxic metal containing proteins could be detected in a single run with high sensitivity (detection limits in the range of 0.0020-2.5 µg/mL) and good repeatability (relative standard deviations lower than 4.5 %). This method was then successfully used to analyze metal (e.g., Pb, Zn, Cu and Fe) binding proteins in the blood of Pb-intoxicated patients, and the results showed a negative correlation between the contents of zinc and lead binding proteins, which was identified to contain hemoglobin subunit. In summary, this work provided a rapid and sensitive tool for screening metal containing proteins in large number of biological samples.

Efficacy and Safety of Acupuncture in Managing COPD: An Overview of Systematic Reviews.

Background: Acupuncture has been used as an adjuvant therapy for Chronic obstructive pulmonary disease (COPD). However, systematic reviews (SRs) and meta-analyses (MAs) have reported inconsistent results and unknown quality. This overview aimed to summarize the current SRs/MAs to provide evidence for the effectiveness and safety of acupuncture in the treatment of COPD. Methods: SRs/MAs were searched via eight databases from their establishment to December 31, 2023. The methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The risk of bias was assessed using the Risk of Bias in Systematic Review (ROBIS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A) to evaluate the reporting quality. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to determine the strength of evidence. In addition, we also conducted an analysis of the acupuncture points used in the primary RCTs. Results: Twenty-two SRs/MAs were included in this overview. Based on the assessment using AMSTAR 2, nineteen SRs/MAs were "critically low". Eight SRs/MAs had a low risk of bias. Based on PRISMA-A, the reporting completeness of eighteen SRs/MAs were more than 70%. As for GRADE assessment, only three outcome measures were of high quality. COPD patients can benefit from moxibustion, acupoint application, acupoint catgut embedding, manual acupuncture, and electroacupuncture, as indicated by effectiveness in measures including lung function, 6MWD, mMRC, CAT, and acute exacerbation. In addition, the efficacy of TENS needed to be further demonstrated. The commonly used acupuncture points in the RCTs include BL13, BL23, and EX-B1. Conclusion: Evidence from SRs showed that acupuncture is beneficial to lung function, acute exacerbation, 6MWD, mMRC and CAT. For SGRQ and brog scale, acupuncture should be used selectively, but this finding should still be taken with caution.

EPSTI1 promotes osteoclast differentiation and bone resorption by PKR/NF-κB signaling.

BACKGROUND: Epithelial stromal interaction 1 (EPSTI1) plays an important role in M1 macrophages, which induce osteoclastogenesis. One recent genome-wide association study (GWAS) involving 426,824 individuals has shown that EPSTI1 is strongly associated with osteoporosis (P < 5E-8). Therefore, we speculate that EPSTI1 participates in the modulation of osteoporosis through osteoclastogenesis. The roles of EPSTI1 in osteoclastogenesis and bone resorption remain unclear. METHODS: Femur specimens were collected from osteoporotic patients and control patients. Immunofluorescence staining was used to detect the expression of EPSTI1 and signaling pathways. The osteoclastic potential of RAW264.7 cells with Sh-EPSTI1 lentivirus infection was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was also used to examine signaling pathways. RESULTS: In this study, EPSTI1 was found to be significantly increased in tartrate-resistant acid phosphatase positive (ACP5+) osteoclasts of bone sections from osteoporotic patients. Next, we identified EPSTI1 as a positive regulator of osteoclastogenesis and osteoclast differentiation capability. Diminished EPSTI1 expression resulted in reduced osteoclastic resorption. Mechanistically, EPSTI1-driven osteoclastogenesis was regulated by NF-κB pathway, which was mediated by the phosphorylation of protein kinase R (p-PKR). Furthermore, EPSTI1 participating in the modulation of osteoporosis via PKR/NF-κB pathway was also verified in the bone samples of osteoporotic patients. CONCLUSIONS: Collectively, our findings suggest that EPSTI1 may regulate osteoclast differentiation and bone resorption through PKR/NF-κB pathway and in vivo experiments are needed to further verify EPSTI1 as the therapy target for osteoporosis.

Low-intensity transcranial focused ultrasound suppresses pain by modulating pain processing brain circuits.

There is an urgent and unmet clinical need to develop non-pharmacological interventions for chronic pain management due to the critical side effects of opioids. Low-intensity transcranial focused ultrasound is an emerging non-invasive neuromodulation technology with high spatial specificity and deep brain penetration. Here, we developed a tightly-focused 128-element ultrasound transducer to specifically target small mouse brains, employing dynamic focus steering. We demonstrate that transcranial focused ultrasound stimulation at pain processing brain circuits can significantly alter pain-associated behaviors in mouse models in vivo. Our findings indicate that a single-session focused ultrasound stimulation to the primary somatosensory cortex (S1) significantly attenuates heat pain sensitivity in wild-type mice and modulates heat and mechanical hyperalgesia in a humanized mouse model of chronic pain in sickle cell disease. Results further revealed a sustained behavioral change associated with heat hypersensitivity by targeting deeper cortical structures (e.g., insula) and multi-session focused ultrasound stimulation to S1 and insula. Analyses of brain electrical rhythms through electroencephalography demonstrated a significant change in noxious heat hypersensitive- and chronic hyperalgesia-associated neural signals following focused ultrasound treatment. Validation of efficacy was carried out through control experiments, tuning ultrasound parameters, adjusting inter-experiment intervals, and investigating effects on age, gender, genotype, and in a head-fixed awake model. Importantly, transcranial focused ultrasound was found to be safe, causing no adverse effects on motor function and brain's neuropathology. In conclusion, the validated proof of principle experimental evidence demonstrates the translational potential of novel focused ultrasound neuromodulation for next-generation pain treatment without adverse effects.

An Investigation of Parameter-Dependent Cell-Type Specific Effects of Transcranial Focused Ultrasound Stimulation Using an Awake Head-Fixed Rodent Model.

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique able to target shallow and deep brain structures with high precision. Previous studies have demonstrated that tFUS stimulation responses are both cell-type specific and controllable through altering stimulation parameters. Specifically, tFUS can elicit time-locked neural activity in regular spiking units (RSUs) that is sensitive to increases in pulse repetition frequency (PRF), while time-locked responses are not seen in fast spiking units (FSUs). These findings suggest a unique capability of tFUS to alter circuit network dynamics with cell-type specificity; however, these results could be biased by the use of anesthesia, which significantly modulates neural activities. In this study, we develop an awake head-fixed rat model specifically designed for tFUS study, and address a key question if tFUS still has cell-type specificity under awake conditions. Using this novel animal model, we examined a series of PRFs and burst duty cycles (DCs) to determine their effects on neuronal subpopulations without anesthesia. We conclude that cell-type specific time-locked and delayed responses to tFUS as well as PRF and DC sensitivity are present in the awake animal model and that despite some differences in response, isoflurane anesthesia is not a major confound in studying the cell-type specificity of ultrasound neuromodulation. We further determine that, in an awake, head-fixed setting, the preferred PRF and DC for inducing time-locked excitation with our pulsed tFUS paradigm are 1500 Hz and 60%, respectively.

Transcranial focused ultrasound activates feedforward and feedback cortico-thalamo-cortical pathways by selectively activating excitatory neurons.

Transcranial focused ultrasound stimulation (tFUS) has been proven capable of altering focal neuronal activities and neural circuits non-invasively in both animals and humans. The abilities of tFUS for cell-type selection within the targeted area like somatosensory cortex have been shown to be parameter related. However, how neuronal subpopulations across neural pathways are affected, for example how tFUS affected neuronal connections between brain areas remains unclear. In this study, multi-site intracranial recordings were used to quantify the neuronal responses to tFUS stimulation at somatosensory cortex (S1), motor cortex (M1) and posterior medial thalamic nucleus (POm) of cortico-thalamo-cortical (CTC) pathway. We found that when targeting at S1 or POm, only regular spiking units (RSUs, putative excitatory neurons) responded to specific tFUS parameters (duty cycle: 6%-60% and pulse repetition frequency: 1500 and 3000 Hz ) during sonication. RSUs from the directly connected area (POm or S1) showed a synchronized response, which changed the directional correlation between RSUs from POm and S1. The tFUS induced excitation of RSUs activated the feedforward and feedback loops between cortex and thalamus, eliciting delayed neuronal responses of RSUs and delayed activities of fast spiking units (FSUs) by affecting local network. Our findings indicated that tFUS can modulate the CTC pathway through both feedforward and feedback loops, which could influence larger cortical areas including motor cortex.

Fabrication of nanoparticle array membranes by integrating semi-crystalline polymer self-assembly with NIPS for water treatment.

The integration of polymer self-assembly with non-solvent induced phase separation (SNIPS) represents a recent advancement in membrane fabrication. This breakthrough allows for the fabrication of membranes with uniformly sized pores, enabling precise and fast separation through a phase inversion process commonly used in industrial fabrication. Currently, block copolymers are used in implementing the SNIPS strategy. In order to facilitate an easier and more flexible fabrication procedure, we employed the widely used semi-crystalline polymer polyvinylidene fluoride (PVDF) as the base material for achieving SNIPS through self-seeding. This process involves filtering the PVDF casting solution to induce microphase separation and generate crystal seeds. Subsequently, NIPS is applied to enable the growth of crystal seeds into uniformly distributed nanoparticles with consistent size and shape, ultimately resulting in a membrane with a uniform pore size. The fabricated membrane exhibited improved flux (2924.67 ± 28.02 L m-2 h-1 at 0.5 bar) and rejection (91% for 500 nm polystyrene particles). Notably, the microphase separation in the casting solution is a distinguishing feature of the SNIPS compared to NIPS. In this study, we found that the microphase separation of semi-crystalline polymers is also crucial for achieving membranes with uniform pore sizes. This finding may extend the potential application of the SNIPS strategy to include semi-crystalline polymers.

Clinical therapeutic effect of self-prescribed Sanhanchushi Tongbi on lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) commonly occurs during spinal surgery; LDH is on the increase in younger patients and is classified as "paralysis" and "back pain." Sanhanchushi Tongbi (SPST) is a customized prescription. It disperses cold, relieves pain, removes cold from the meridians and viscera, and treats neuropathic pain. However, few studies have investigated its mechanism of pain relief. AIM: To observe the clinical therapeutic effects on LDH treated with self-prescribed SPST. METHODS: A total of 211 patients with LDH syndrome were divided into two groups: 107 patients in the control group were treated with conventional massage combined with traction, and 104 patients in the observation group were treated with a combination of the control regimen and self-prescribed oral SPST. The patients were treated for 4 wk. Indices of traditional Chinese medicine (TCM) syndrome score and serum inflammatory factor levels were measured. RESULTS: After therapy, the TCM syndrome score in the observation group was significantly lower than that in the control group (P < 0.05). The main symptoms, clinical signs, daily activities, and Japanese Orthopedic Association scores in the observation group were significantly higher than those in the control group after therapy (P < 0.05). The levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein were lower in the observation group than in the control group (P < 0.05). In the observation group, superoxide dismutase levels were significantly higher, whereas malondialdehyde levels were significantly lower, compared with the control group (P < 0.05). The overall efficacy rate in the observation group was 96.15%, which was substantially higher than that in the control group (88.79%; P < 0.05). CONCLUSION: Self-prescribed SPST can reduce the levels of inflammatory and pain-causing factors as well as lumbar pain in patients with LDH.

Effect of temperature and pre-stretch on the dynamic performance of dielectric elastomer minimum energy structure.

Dielectric Elastomer Minimum Energy Structures (DEMES) have the ability of actively adjusting their shape to accommodate complex scenarios, understanding the actuation mechanism of DEMES is essential for their effective design and control, which has rendered them a focus of research in the field of soft robotics. The actuation ability of DEMES is usually influenced by external conditions, among which the electromechanical properties of DE materials are highly sensitive to temperature changes, and the pre-stretch ratio of DE materials has a significant impact on the dynamic performance of DEMES. Therefore, it is necessary to study the effects of temperature and pre-stretch ratio on the nonlinear dynamic behavior of DEMES. In this paper, in response to the lack of research on the influence of DE pre-stretch ratio on the actuation characteristics of DEMES, this paper proposes a systematic modeling and analysis framework that comprehensively considers pre-stretch factors, temperature factors, and viscoelastic factors, and establishes the motion control equation of DEMES affected by the coupling effect of DE pre-stretch ratio and temperature. The proposed analytical framework is used to analyze the evolution of the electromechanical response of DEMES under voltage excitation under the coupling of DE pre-stretch ratio and temperature. The results indicate that the bending angle, inelastic deformation, resonant frequency, and dynamic stability of DEMES can be jointly adjusted by the DE pre-stretch ratio and ambient temperature. A low pre-stretch ratio of DE can lead to dynamic instability of DEMES, while appropriate temperature conditions and higher pre-stretch ratios can significantly improve the actuation ability of DEMES. This can provide theoretical guidance for the design and deformation control of DEMES.

Immuno-Nanocomplexes Target Heterogenous Network of Inflammation and Immunity in Myocardial Infarction.

Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti-AMI therapeutics to resolve reactive oxygen species (ROS)-proinflammatory neutrophils-specific-inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils-S100A8/A9-inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall CuxO nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)-conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro-inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.

Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.

BACKGROUND: Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive. METHODS: KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines. RESULTS: In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both KrasLSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients. CONCLUSION: We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Polydimethylsiloxane enabled triple-action water-resistant coating with desirable relaxation rate in clear aligner.

Clear aligners undergo rapid stress relaxation in warm, moist oral environments, compromising therapeutic effectiveness and longevity of treatment. To develop an innovative multilayer composite material with improved stability and reduced stress release, we have engineered an innovative coating characterized by the surface aggregation of polydimethylsiloxane (PDMS), which imparts a pronounced hydrophobic effect. In addition, the chemically and physically cross-linked structure of the coating reduces the free volume created by molecular chain rearrangement owing to the presence of water molecules, thereby minimizing water penetration into the coating. Concurrently, the coating's internal structure is enriched with numerous polar functional groups to capture water molecules that penetrate into the inside of the coating. Through combination of these mechanisms, water molecules are effectively sequestered, thereby impeding their penetration into the polyethylene terephthalate glycol (PETG) substrate. The impact of the polydimethylsiloxane content on the triple-action water-resistance mechanisms was thoroughly examined using attenuated total reflection (ATR)-Fourier transform infrared (FTIR), water absorption rate, water swelling rate, and X-ray photoelectron spectroscopy. The low surface energy cross-linked polyurethane coating is applied to the polyethylene terephthalate glycol (PETG) substrate to create a novel composite material with specific mechanical properties and reduced stress relaxation. The composite material remains stable in simulated oral environment with linear swelling rate of 0.58 % upon water absorption. Additionally, the stress release rate of the composite material within 336 h is notably lower (23.64 %) than that of PETG (62.29 %).