Alternate levels versus all levels mini-plate fixation in C3-6 cervical laminoplasty: a retrospective comparative study.

OBJECTIVE: The purpose of this study is to compare radiological and clinical outcomes between alternate levels (C4 and C6) and all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. METHODS: Ninety-six patients who underwent C3-6 unilateral open-door laminoplasty with alternate levels mini-plate fixation (54 patients in group A) or all levels mini-plate fixation (42 patients in group B) between September 2014 and September 2019 were reviewed in this study. Radiologic and clinical outcomes were assessed. Clinical results included Visual Analogue Scale (VAS) of axial neck pain and Japanese Orthopedic Association (JOA) score. Radiographic results included cervical range of motion (ROM), cervical curvature index (CCI), and the spinal canal expansive parameters including open angle, anteroposterior diameter (APD), and Pavlov`s ratio. RESULTS: There was no significant difference in VAS, JOA score, ROM, and CCI between two groups. There was no significant difference in canal expansion postoperatively between two groups. However, open angle, APD, and Pavlov`s ratio in group A decreased significantly during the follow-up. In group B, APD, Pavlov`s ratio, and open angle were maintained until the final follow-up. There was no hardware failure or lamina reclosure occurred in both groups during the follow-up. The mean cost of group B was higher than that of group A. CONCLUSIONS: Despite the differences in the maintenance of canal expansion, alternate levels mini-plate fixation can achieve similar clinical outcomes as all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. As evidenced in this study, we believe C3-6 laminoplasty with alternate levels (C4 and C6) mini-plate fixation is an economical, effective, and safe treatment method.

Application of biomacromolecule-based passive penetration enhancement technique in superficial tumor therapy: A review.

Transdermal drug delivery (TDD) has shown great promise in superficial tumor therapy due to its noninvasive and avoidance of the first-pass effect. Especially, passive penetration enhancement technique (PPET) provides the technical basis for TDD by temporarily altering the skin surface structure without requiring external energy. Biomacromolecules and their derived nanocarriers offer a wide range of options for PPET development, with outstanding biocompatibility and biodegradability. Furthermore, the abundant functional groups on biomacromolecule surfaces can be modified to yield functional materials capable of targeting specific sites and responding to stimuli. This enables precise drug delivery to the tumor site and controlled drug release, with the potential to replace traditional drug delivery methods and make PPET-related personalized medicine a reality. This review focuses on the mechanism of biomacromolecules and nanocarriers with skin, and the impact of nanocarriers' surface properties of nanocarriers on PPET efficiency. The applications of biomacromolecule-based PPET in superficial tumor therapy are also summarized. In addition, the advantages and limitations are discussed, and their future trends are projected based on the existing work of biomacromolecule-based PPET.

Pathology of pain and its implications for therapeutic interventions.

Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.

Biocompatible Electrical and Optical Interfaces for Implantable Sensors and Devices.

Implantable bioelectronics hold tremendous potential in the field of healthcare, yet the performance of these systems heavily relies on the interfaces between artificial machines and living tissues. In this paper, we discuss the recent developments of tethered interfaces, as well as those of non-tethered interfaces. Among them, systems that study neural activity receive significant attention due to their innovative developments and high relevance in contemporary research, but other functional types of interface systems are also explored to provide a comprehensive overview of the field. We also analyze the key considerations, including perforation site selection, fixing strategies, long-term retention, and wireless communication, highlighting the challenges and opportunities with stable, effective, and biocompatible interfaces. Furthermore, we propose a primitive model of biocompatible electrical and optical interfaces for implantable systems, which simultaneously possesses biocompatibility, stability, and convenience. Finally, we point out the future directions of interfacing strategies.

Clinical efficacy and imaging analysis of oblique lateral lumbar interbody fusion in the treatment of different types of lumbar intervertebral foramen stenosis.

PURPOSE: To analyze and study the clinical efficacy and imaging indexes of oblique lateral lumbar interbody fusion (OLIF) in the treatment of lumbar intervertebral foramen stenosis(LFS) caused by different causes. METHOD: 33 patients with LFS treated with OLIF from January 2018 to May 2022 were reviewed. Oswestry Dysfunction Index (ODI) and visual analogue scale (VAS) were calculated before and after operation. Segmental lordotic angle (SLA), lumbar lordotic angle (LLA) and segmental scoliosis angle (SSA), disc height (DH), posterior disc height (PDH), lateral disc height (LDH), foraminal height (FH), foramen width (FW) and foraminal cross-sectional area (FSCA) were measured before and after operation. RESULT: The VAS and ODI after operation were significantly improved as compared with those before operation. Compared with pre-operation, the DH, PHD increased by 67.6%, 94.6%, LDH increased by 107.4% (left), 101.7% (right), and FH increased by 30.2% (left), 34.5% (right). The FSCA increased by 93.1% (left), 89.0% (right), and the FW increased by 137.0% (left), 149.6% (right). The postoperative SSA was corrected by 74.5%, the postoperative SLA, LLA were corrected by 70.2%, 38.1%, respectively. All the imaging indexes were significantly improved (p < 0.01). CONCLUSION: The clinical efficacy and imaging data of OLIF in the treatment of LFS caused by low and moderate lumbar spondylolisthesis, intervertebral disc bulge and reduced intervertebral space height, degenerative lumbar scoliosis, articular process hyperplasia or dislocation have been well improved. OLIF may be one of the better surgical treatments for LFS caused by the above conditions.

Impaired neuronal macroautophagy in the prelimbic cortex contributes to comorbid anxiety-like behaviors in rats with chronic neuropathic pain.

A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL. Chemogenetic inactivation of this comorbid anxiety-related neuronal ensemble relieved pain-induced anxiety-like behaviors. Rescuing macroautophagy impairment in this neuronal ensemble relieved chronic pain-associated anxiety and mechanical allodynia and restored synaptic homeostasis at the molecular level. By contrast, artificial disruption of macroautophagy induced early-onset co-morbid anxiety in neuropathic rats, but not general anxiety in normal rats. Taken together, our work identifies causal linkage between PrL neuronal macroautophagy dysfunction and comorbid anxiety in neuropathic pain and provides novel insights into the role of PrL by differentiating its contribution in pain-induced comorbid anxiety from its modulation over general anxiety-like behaviors.Abbreviation: AAV: adeno-associated viruses; ACC: anterior cingulate cortex; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; CAMK2/CaMKII: calcium/calmodulin-dependent protein kinase II; CNO: clozapine-N-oxide; CQ: chloroquine; DIA: data independent acquisition; DIO: double floxed inverse orf; DLG4/PSD-95: discs large MAGUK scaffold protein 4; Dox: doxycycline; GABA: γ-aminobutyric acid; GFP: green fluorescent protein; GO: gene ontology; Gi: inhibitory guanine nucleotide-binding proteins; HsCHRM4/M4D: human cholinergic receptor muscarinic 4; HsSYN: human synapsin; KEGG: Kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; LC3-II: PE conjugated microtubule-associated protein 1 light chain3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mPFC: medial prefrontal cortex; P2A: 2A self-cleaving peptide; PPI: protein-protein interaction networks; PrL: prelimbic cortex; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; rtTA: reverse tetracycline-transactivator; SDS-PAGE: sodium dodecylsulfate-polyacrylamide gel electrophoresis; SHANK3: SH3 and multiple ankyrin repeat domains 3; SLC1A1/EAAC1: solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, systemXag), member 1; SNAP23: synaptosomal-associated protein 23; SNI:spared nerve injury; SQSTM1/p62: sequestosome 1; SYT3: synaptotagmin 3; TRE: tetracycline-responsive element; TRE3G: third-generation tetracycline-responsive element.

Bioinspired photoelectrochemical NADH regeneration based on a molecular catalyst-modified photocathode.

For photoelectrochemical NADH regeneration, an electrode-supported "lipid bilayer membrane" photocathode based on a p-Si semiconductor, an electron transport mediator (OBV2+), and a [Rh(Cp*)(bpy)Cl]+ catalyst was constructed by self-assembly. Mechanistic study shows that OBV2+ can enhance the charge transfer between the semiconductor and catalyst, leading to a significant improvement of the NADH photo-regeneration rate.

Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes.

Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.

Network of Soil Fungi and the Microfauna Community under Diverse Anthropic Disturbances under Chrysopogon zizanioides Planting in the Reservoir.

The reservoir coastal zone is the transitional zone between the terrestrial ecosystem and the aquatic ecosystem. Soil is an essential part of the terrestrial ecosystem and vital for life on Earth. To understand the composition and diversity of the soil eukaryotic microbial community under the background of artificial planting of Chrysopogon zizanioides in various habitats after reservoir construction, including the original habitat (OH), the hydro-fluctuation belt (HB), and the road slope (RS), and to analyze the interaction between the main groups of eukaryotic microorganisms, this study conducted 18S rDNA amplification high-throughput sequencing of the soil eukaryotic microbial community. The study found that the dominant phylum of eukaryotic microorganisms in the three habitats was consistent, but there were significant differences in the community and diversity of eukaryotic microorganisms in the three habitats. The differences in fungal communities between sample sites were greater than those of soil microfauna. Correlation analysis showed that nitrogen, phosphorus, and organic matter were significantly correlated with eukaryotic microbial diversity, with alkaline-hydrolyzed nitrogen and total phosphorus significantly correlated with fungal communities and pH and water content correlated with soil microfauna. Co-occurrence network analysis found that the interactions between fungi and the correlation between fungi and soil microfauna dominated the eukaryotic microbial community, and the interactions between eukaryotic microbes in different habitats were dominated by positive correlations. After the construction of the reservoir, the newly formed hydro-fluctuation belt reduced the types of interrelationships between fungi and microfauna compared to the original habitat. The road slope provided protection of the supporting project for the reservoir construction, although there was also planted vegetation. Eukaryotic microbes declined significantly due to the damage to and loss of the organic layer, and the decline in microfauna was the most significant, resulting in a simple structure of the soil food web, which affects the function and stability of the soil ecosystem.

Dynamic Changes of the Infralimbic Cortex and Its Regulation of the Prelimbic Cortex in Rats with Chronic Inflammatory Pain.

The prelimbic cortex (PL) is actively engaged in pain modulation. The infralimbic cortex (IL) has been reported to regulate the PL. However, how this regulation affects pain remains unclear. In the present study, we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli, but a temporary hypo-function of the IL by in vivo electrophysiological recording in rats with peripheral inflammation. Manipulation of the PL or IL had opposite effects on thermal hyperalgesia. Furthermore, the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL. Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia, whereas its inhibition exacerbated chronic pain. Overall, our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain: hypo-function of the IL leads to hyperactivity of the PL, which regulates thermal hyperalgesia, and thus contributes to the chronicity of pain.

How to Choose Surgical Corridor in Left Oblique Approach Lumbar Interbody Fusion at the L5-S1 Segment: A Prospective Cohort Study.

OBJECTIVE: There are 2 surgical corridors to L5-S1 lumbar interbody fusion via the left oblique approach: anterior to psoas-oblique lateral interbody fusion (ATP-OLIF) and oblique-anterior lumbar interbody fusion (O-ALIF). The aim of this study was to evaluate criteria to guide the selection of surgical corridors for L5-S1 lumbar interbody fusion via the left oblique approach. METHODS: According to the structure of L5-S1 segment left common iliac vein (LCIV) in axial magnetic resonance image, the LCIV was divided into 6 types. O-ALIF was performed for type I and type II. ATP-OLIF was performed for type A and type B. For sexually active men, ATP-OLIF was chosen. Between April 2020 and April 2022, 22 patients were assigned to ATP-OLIF or O-ALIF based on the type of LCIV. Clinical outcomes and radiographic outcomes were assessed. RESULTS: There were 11 cases in O-ALIF group (type I, n = 10; type II, n = 1) and 11 cases in ATP-OLIF group (type A, n = 8; type B, n = 3). No differences were observed in clinical outcomes (Oswestry Disability Index, VAS, and complication rate); radiographic outcomes (mean disk height and segmental lordosis angle); length of hospital stay; operation time; and blood loss. No vascular injury occurred in either group. CONCLUSIONS: This may be an appropriate criterion to guide the selection of surgical corridor for L5-S1 lumbar interbody fusion through the left oblique approach. O-ALIF was performed for type I and type II. ATP-OLIF was performed for type A and type B. For sexually active men, ATP-OLIF was chosen. According to this standard, the operation can be performed safely and with good clinical results.

Synthesis of Tubular Hydroxyapatite and Its Application in Polycaprolactone Scaffold Materials.

Nano-hydroxyapatite (HAp) is an ideal material in the field of biomedicine due to its good biocompatibility and bioactivity. However, a significant drawback of pure HAp materials is their inferior mechanical properties. Therefore, in this rigorous investigation, the optimal calcium-to-phosphorus ratio for the synthesis of HAp was meticulously delineated, followed by its nuanced modification using KH550 (γ-aminopropyltriethoxysilane). This was further amalgamated with polycaprolactone (PCL) with the aim of providing a superior material alternative within the domain of bone scaffold materials. The post-modified HAp demonstrated enhanced interfacial compatibility with PCL, bestowing the composite with superior mechanical characteristics, notably a peak bending strength of 6.38 ± 0.037 MPa and a tensile strength of 3.71 ± 0.040 MPa. Scanning electron microscope (SEM) imagery revealed an intriguing characteristic of the composite: an initial ascension in porosity upon HAp integration, subsequently followed by a decline. Beyond this, the composite not only exhibited stellar auto-degradation prowess but also realized a sustained release cycle of 24 h, markedly optimizing drug utility efficiency. A kinetic model for drug dispensation was developed, positing an adherence to a pseudo-second-order kinetic principle. In tandem, through the formulation of an intra-particle diffusion model, the diffusion mechanisms pre- and post-modification were deeply probed. Cytotoxicity assays underscored the composite's exemplary biocompatibility. Such findings accentuate the vast potential of the modified HAp-PCL composite in bone tissue engineering, heralding a novel and efficacious avenue for impending bone defect amelioration.

Ventral Hippocampal CA1 Pyramidal Neurons Encode Nociceptive Information.

As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats. Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions: the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli, whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties. Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors. Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats, whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain. These results provide direct evidence for the representations of nociceptive information in vCA1.

Adherence Behaviors and Related Factors Among Elderly Hypertensive Patients in China: Evidence from the China Health and Retirement Longitudinal Study.

Background: Non-adherence or partial adherence is the main reason for poor therapeutic effect of hypertension. This paper aims to assess adherence behaviors and related factors among elderly hypertensive patients in China. Methods: Participants aged ≥60 years, with hypertension, and with complete data in 2018 interviews of the China Health and Retirement Longitudinal Study (CHARLS) were included. The adherence behaviors included medication, blood pressure monitoring and the combined adherence behaviors. Referring to the social-ecological theory, correlates of adherence behaviors were divided into three layers, namely demographic characteristics, health behaviors, living environment and retirement. Univariate and multivariable logistic regression models were performed to identify factors of adherence behaviors. Results: The prevalence of medication adherence (76.58%) was higher than that of blood pressure monitoring adherence (20.08%), and the full adherence rate was 18.53%. Self-rated health status, smoking status, living area, and health education status were detected to be associated with medication adherence and blood pressure monitoring adherence (all p < 0.05). Gender, sleep duration, health examination, and physical exercise were also detected to be associated with blood pressure monitoring adherence (all p < 0.05). Self-rated health status and health education status were detected to be associated with partially and fully adherence, while age, living area, and life satisfaction were detected to be associated with partially adherence, smoking status, sleep duration, health examination, and pension reliance were detected to be associated with fully adherence (all p < 0.05). Conclusion: Our study reveals the poor adherence behaviors of elderly hypertensive patients in China. This is most evident among those who were male, 60-69 years old, living in rural areas, self-reported being healthier, those without health examination and health education. Targeting these vulnerable populations, we suggest to strengthen health education, increase the publicity of basic public health services and enhance the self-management ability of hypertensive patients.

Research on Development 3D Ground Penetrating Radar Acquisition and Control Technology for Road Underground Diseases with Dual-Band Antenna Arrays.

This paper describes the development of a new 3D ground-penetrating radar (GPR) acquisition and control technology for road underground diseases with dual-band antenna arrays. The 3D GPR system can be mounted on a vehicle-loading device and used by vehicles to detect road underground diseases at regular speeds. Compared with existing 3D GPR systems, this new type of 3D GPR has the following design features: it has dual-band antenna arrays, including a 16-channel 400 MHz antenna array and an 8-channel 200 MHz antenna array, which not only improves the detection efficiency, but also effectively balances the detection depth and detection resolution. A novel antenna switching method for time division step multiplexing (TDSM) is realized via field programmable gate array (FPGA), which not only avoids the crosstalk of antenna echo signals of different frequencies, but also ensures the interval of the same antenna working time. By combining the advantages of the FPGA and micro-control unit (MCU), and utilizing the high-speed transmission of the network port, the high-speed real-time transmission of the 3D GPR echo data is achieved. Finally, the integration of all software and hardware verified the correctness of the system, with good results.

Classification of subtypes and identification of dysregulated genes in sepsis.

Background: Sepsis is a clinical syndrome with high mortality. Subtype identification in sepsis is meaningful for improving the diagnosis and treatment of patients. The purpose of this research was to identify subtypes of sepsis using RNA-seq datasets and further explore key genes that were deregulated during the development of sepsis. Methods: The datasets GSE95233 and GSE13904 were obtained from the Gene Expression Omnibus database. Differential analysis of the gene expression matrix was performed between sepsis patients and healthy controls. Intersection analysis of differentially expressed genes was applied to identify common differentially expressed genes for enrichment analysis and gene set variation analysis. Obvious differential pathways between sepsis patients and healthy controls were identified, as were developmental stages during sepsis. Then, key dysregulated genes were revealed by short time-series analysis and the least absolute shrinkage and selection operator model. In addition, the MCPcounter package was used to assess infiltrating immunocytes. Finally, the dysregulated genes identified were verified using 69 clinical samples. Results: A total of 898 common differentially expressed genes were obtained, which were chiefly related to increased metabolic responses and decreased immune responses. The two differential pathways (angiogenesis and myc targets v2) were screened on the basis of gene set variation analysis scores. Four subgroups were identified according to median expression of angiogenesis and myc target v2 genes: normal, myc target v2, mixed-quiescent, and angiogenesis. The genes CHPT1, CPEB4, DNAJC3, MAFG, NARF, SNX3, S100A9, S100A12, and METTL9 were recognized as being progressively dysregulated in sepsis. Furthermore, most types of immune cells showed low infiltration in sepsis patients and had a significant correlation with the key genes. Importantly, all nine key genes were highly expressed in sepsis patients. Conclusion: This study revealed novel insight into sepsis subtypes and identified nine dysregulated genes associated with immune status in the development of sepsis. This study provides potential molecular targets for the diagnosis and treatment of sepsis.

HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice.

Chronic pain is a significant health problem worldwide. Recent evidence has suggested that the ventral hippocampus is dysfunctional in humans and rodents, with decreased neuronal excitability and connectivity with other brain regions, parallel pain chronicity, and persistent nociceptive hypersensitivity. But the molecular mechanisms underlying hippocampal modulation of pain remain poorly elucidated. In this study, we used ex vivo whole-cell patch-clamp recording, immunofluorescence staining, and behavioral tests to examine whether hyperpolarization-activated cyclic nucleotide-gated channels 2 (HCN2) in the ventral hippocampal CA1 (vCA1) were involved in regulating nociceptive perception and CFA-induced inflammatory pain in mice. Reduced sag potential and firing rate of action potentials were observed in vCA1 pyramidal neurons from CFA-injected mice. Moreover, the expression of HCN2, but not HCN1, in vCA1 decreased in mice injected with CFA. HCN2 knockdown in vCA1 pyramidal neurons induced thermal hypersensitivity, whereas overexpression of HCN2 alleviated thermal hyperalgesia induced by intraplantar injection of CFA in mice. Our findings suggest that HCN2 in the vCA1 plays an active role in pain modulation and could be a promising target for the treatment of chronic pain.

The impact of climate disaster on international trade: Evidence from developed and developing countries.

A climate disaster can be devastating, but its challenges and losses provide some opportunities to other countries. Therefore, in this paper, we examine the impact of climate risk on international trade with a particular focus on developed and developing countries. Using a large sample of 160 countries between 2006 and 2019, we find that climate disaster is positively associated with high international trade. An increase in the climate disaster index will lead to an increase of about 5.9% in imports as a proportion of GDP. This is significant given that the mean of imports of the sample countries is 48%. Regarding the flow of trade, importation is likely to increase by about 6.7% and export to decrease by 0.65% after the occurrence of climate disasters in developing countries. Conversely, we did not find significant changes in imports and a weak association with exports for developed countries. We attribute this differential impact of climate disasters between developed and developing countries to the preparedness and risk mitigation mechanism in developed countries. The result suggests that the long-term effect of climate disasters increasing overall international trade is due to increasing imports in developing countries. Additional analyses demonstrate the robustness of these results to different model specifications and measurements of variables. Our results imply that climate change and its associated natural disasters offer more trade opportunities for developed countries than developing countries, highlighting the climate injustices between the high and low climate change contributors.

Multisubcellular organelle-targeting nanoparticle for synergistic chemotherapy and photodynamic/photothermal tumor therapy.

Background: The subcellular organelle-targeting strategy has attracted wide attention for a variety of reasons, including strong specificity, high accuracy, low dose administration and few side effects. It is an important and challenging task to explore the multisubcellular organelle-targeting strategy to achieve effective tumor treatment. Materials & methods: Using bovine serum albumin as a nanoreactor, BSA/Cu/NQ/IR780/DOX nanoparticles (NPs) were constructed via drug-induced protein self-assembly. Folic acid was then coupled to the surface of NPs to prepare folate receptor-targeted FA-BSA/Cu/NQ/IR780/DOX NPs. Results & conclusion: The FA-BSA/Cu/NQ/IR780/DOX NPs exhibit multifunctional properties, including multisubcellular organelle-targeting, induction of response release in the tumor microenvironment, fluorescence imaging capabilities and potential for synergistic chemotherapy and photodynamic/photothermal tumor therapy.

The subcellular organelle-targeting strategy has attracted wide attention for a variety of reasons, including strong specificity, high accuracy, low dose administration and few side effects. Previous research has been mostly restricted to one or two subcellular organelle therapies. Despite promising results, the impact of these studies is limited by the hostile conditions of lysosomes, drug efflux facilitated by P-glycoprotein (P-gp), and the expression of antiapoptotic factors, all of which undermine the effectiveness of the treatments. Therefore, it is an important and challenging task to explore the multisubcellular organelle-targeting strategy to achieve effective tumor treatment. Herein, a versatile nanoparticle was designed and constructed to target multiple subcellular organelles, respond to stimuli in the tumor microenvironment, enable fluorescence imaging and facilitate synergistic chemotherapy and photodynamic/photothermal tumor therapy.

Advances in Natural Polymer-Based Transdermal Drug Delivery Systems for Tumor Therapy.

As an alternative to traditional oral and intravenous injections with limited efficacy, transdermal drug delivery (TDD) has shown great promise in tumor treatment. Over the past decade, natural polymers have been designed into various nanocarriers due to their excellent biocompatibility, biodegradability, and easy availability, providing more options for TDD. In addition, surface functionalization modification of the rich functional groups of natural polymers, which in turn are developed into targeted and stimulus-responsive functional materials, allows precise delivery of drugs to tumor sites and release of drugs in response to specific stimuli. It not only improves the treatment efficiency of tumor but also reduces the toxic and side effects to normal tissues. Therefore, the development of natural polymer-based TDD (NPTDD) systems has great potential in tumor therapy. In this review, the mechanism of NPTDD systems such as penetration enhancers, nanoparticles, microneedles, hydrogels and nanofibers prepared from hyaluronic acid, chitosan, sodium alginate, cellulose, heparin and protein, and their applications in tumor therapy are overviewed. This review also outlines the future prospects and current challenges of NPTDD systems for local treatment tumors.