Large potential of strengthening the land carbon sink in China through anthropogenic interventions.

The terrestrial ecosystem in China mitigates 21%-45% of the national contemporary fossil fuel CO2 emissions every year. Maintaining and strengthening the land carbon sink is essential for reaching China's target of carbon neutrality. However, this sink is subject to large uncertainties due to the joint impacts of climate change, air pollution, and human activities. Here, we explore the potential of strengthening land carbon sink in China through anthropogenic interventions, including forestation, ozone reduction, and litter removal, taking advantage of a well-validated dynamic vegetation model and meteorological forcings from 16 climate models. Without anthropogenic interventions, considering Shared Socioeconomic Pathways (SSP) scenarios, the land sink is projected to be 0.26-0.56 Pg C a-1 at 2060, to which climate change contributes 0.06-0.13 Pg C a-1 and CO2 fertilization contributes 0.08-0.44 Pg C a-1 with the stronger effects for higher emission scenarios. With anthropogenic interventions, under a close-to-neutral emission scenario (SSP1-2.6), the land sink becomes 0.47-0.57 Pg C a-1 at 2060, including the contributions of 0.12 Pg C a-1 by conservative forestation, 0.07 Pg C a-1 by ozone pollution control, and 0.06-0.16 Pg C a-1 by 20% litter removal over planted forest. This sink can mitigate 90%-110% of the residue anthropogenic carbon emissions in 2060, providing a solid foundation for the carbon neutrality in China.

Evaluation of artificial intelligence-powered screening for sexually transmitted infections-related skin lesions using clinical images and metadata.

BACKGROUND: Sexually transmitted infections (STIs) pose a significant global public health challenge. Early diagnosis and treatment reduce STI transmission, but rely on recognising symptoms and care-seeking behaviour of the individual. Digital health software that distinguishes STI skin conditions could improve health-seeking behaviour. We developed and evaluated a deep learning model to differentiate STIs from non-STIs based on clinical images and symptoms. METHODS: We used 4913 clinical images of genital lesions and metadata from the Melbourne Sexual Health Centre collected during 2010-2023. We developed two binary classification models to distinguish STIs from non-STIs: (1) a convolutional neural network (CNN) using images only and (2) an integrated model combining both CNN and fully connected neural network (FCN) using images and metadata. We evaluated the model performance by the area under the ROC curve (AUC) and assessed metadata contributions to the Image-only model. RESULTS: Our study included 1583 STI and 3330 non-STI images. Common STI diagnoses were syphilis (34.6%), genital warts (24.5%) and herpes (19.4%), while most non-STIs (80.3%) were conditions such as dermatitis, lichen sclerosis and balanitis. In both STI and non-STI groups, the most frequently observed groups were 25-34 years (48.6% and 38.2%, respectively) and heterosexual males (60.3% and 45.9%, respectively). The Image-only model showed a reasonable performance with an AUC of 0.859 (SD 0.013). The Image + Metadata model achieved a significantly higher AUC of 0.893 (SD 0.018) compared to the Image-only model (p < 0.01). Out of 21 metadata, the integration of demographic and dermatological metadata led to the most significant improvement in model performance, increasing AUC by 6.7% compared to the baseline Image-only model. CONCLUSIONS: The Image + Metadata model outperformed the Image-only model in distinguishing STIs from other skin conditions. Using it as a screening tool in a clinical setting may require further development and evaluation with larger datasets.

The Effects of External Interfaces on Hydrophobic Interactions I: Smooth Surface.

External interfaces, such as the air-water and solid-liquid interfaces, are ubiquitous in nature. Hydrophobic interactions are considered the fundamental driving force in many physical and chemical processes occurring in aqueous solutions. It is important to understand the effects of external interfaces on hydrophobic interactions. According to the structural studies on liquid water and the air-water interface, the external interface primarily affects the structure of the topmost water layer (interfacial water). Therefore, an external interface may affect hydrophobic interactions. The effects of interfaces on hydrophobicity are related not only to surface molecular polarity but also to the geometric characteristics of the external interface, such as shape and surface roughness. This study is devoted to understanding the effects of a smooth interface on hydrophobicity. Due to hydrophobic interactions, the solutes tend to accumulate at external interfaces to maximize the hydrogen bonding of water. Additionally, these can be demonstrated by the calculated potential mean forces (PMFs) using molecular dynamic (MD) simulations.

A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Microplastic detection and remediation through efficient interfacial solar evaporation for immaculate water production.

Freshwater scarcity and microplastics (MPs) pollution are two concerning and intertwined global challenges. In this work, we propose a "one stone kills two birds" strategy by employing an interfacial solar evaporation platform (ISEP) combined with a MPs adsorbent. This strategy aims to produce clean water and simultaneously enhance MPs removal. Unlike traditional predecessors, our ISEP generates condensed water free from MPs contamination. Additionally, the photothermally driven interfacial separation process significantly improves the MPs removal performance. We observed a removal ratio increase of up to 5.5 times compared to previously reported MPs adsorbents. Thus, our rationally-designed ISEP holds promising potential to not only mitigate the existing water scarcity issue but also remediate MPs pollution in natural water environments.

Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Cognatishimia coralii sp. nov., a marine bacterium isolated from seawater surrounding corals.

Coral reefs are declining due to the rising seawater temperature. Bacteria within and surrounding corals play key roles in maintaining the homeostasis of the coral holobiont. Research on coral-related bacteria could provide benefits for coral reef restoration. During the isolation of coral-associated bacteria, a Gram-stain-negative, motile bacterium (D5M38T) was isolated from seawater surrounding corals in Daya Bay, Shenzhen, PR China. Phylogenetic analysis revealed that strain D5M38T represents a novel species in the genus Cognatishimia. The temperature range for strain D5M38T growth was 10-40 °C, and the optimum temperature was 37 °C. The salinity range for the growth of this isolate was from 0 to 4.0 %, with an optimal salinity level of 0.5 %. The pH range necessary for strain D5M38T growth was between pH 5.0 and 9.0, with an optimal pH being 7.5. The predominant fatty acid was summed feature 8 (65.0 %). The major respiratory quinone was Q-10. The DNA G+C content was 56.8 %. The genome size was 3.88 Mb. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strain D5M38T and its two closest neighbours, Cognatishimia activa LMG 29900T and Cognatishimia maritima KCTC 23347T, were 73.2/73.6%, 73.2/73.6% and 19.7/19.5%, respectively. Strain D5M38T was clearly distinct from its closest neighbours C. activa LMG 29900T and C. maritima KCTC 23347T, with 16S rRNA gene sequence similarity values of 97.5 and 97.3 %, respectively. The phylogenetic analysis, along with the ANI, AAI, and dDDH values, demonstrated that strain D5M38T is a member of the genus Cognatishimia, and is distinct from the other two recognized species within this genus. The physiological, biochemical and chemotaxonomic characteristics also supported the species novelty of strain D5M38T. Thus, strain D5M38T is considered to be classified as representing a novel species in the genus Cognatishimia, for which the name Cognatishimia coralii sp. nov. is proposed. The type strain is D5M38T (=MCCC 1K08692T=KCTC 8160T).

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

The Dependence of Hydrophobic Interactions on the Shape of Solute Surface.

According to our recent studies on hydrophobicity, this work is aimed at understanding the dependence of hydrophobic interactions on the shape of a solute's surface. It has been observed that dissolved solutes primarily affect the structure of interfacial water, which refers to the top layer of water at the interface between the solute and water. As solutes aggregate in a solution, hydrophobic interactions become closely related to the transition of water molecules from the interfacial region to the bulk water. It is inferred that hydrophobic interactions may depend on the shape of the solute surface. To enhance the strength of hydrophobic interactions, the solutes tend to aggregate, thereby minimizing their surface area-to-volume ratio. This also suggests that hydrophobic interactions may exhibit directional characteristics. Moreover, this phenomenon can be supported by calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations, where different surfaces, such as convex, flat, or concave, are associated with a sphere. Furthermore, this concept can be extended to comprehend the molecular packing parameter, commonly utilized in studying the self-assembly behavior of amphiphilic molecules in aqueous solutions.

Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Scalable multifunctional MOFs-textiles via diazonium chemistry.

Cellulose fiber-based textiles are ubiquitous in daily life for their processability, biodegradability, and outstanding flexibility. Integrating cellulose textiles with functional coating materials can unlock their potential functionalities to engage diverse applications. Metal-organic frameworks (MOFs) are ideal candidate materials for such integration, thanks to their unique merits, such as large specific surface area, tunable pore size, and species diversity. However, achieving scalable fabrication of MOFs-textiles with high mechanical durability remains challenging. Here, we report a facile and scalable strategy for direct MOF growth on cotton fibers grafted via the diazonium chemistry. The as-prepared ZIF-67-Cotton textile (ZIF-67-CT) exhibits excellent ultraviolet (UV) resistance and organic contamination degradation via the peroxymonosulfate activation. The ZIF-67-CT is also used to encapsulate essential oils such as carvacrol to enable antibacterial activity against E. coli and S. aureus. Additionally, by directly tethering a hydrophobic molecular layer onto the MOF-coated surface, superhydrophobic ZIF-67-CT is achieved with excellent self-cleaning, antifouling, and oil-water separation performances. More importantly, the reported strategy is generic and applicable to other MOFs and cellulose fiber-based materials, and various large-scale multi-functional MOFs-textiles can be successfully manufactured, resulting in vast applications in wastewater purification, fragrance industry, and outdoor gears.

Malleable, Ultrastrong Antibacterial Thermosets Enabled by Guanidine Urea Structure.

Dynamic covalent polymers (DCPs) that strike a balance between high performance and rapid reconfiguration have been a challenging task. For this purpose, a solution is proposed in the form of a new dynamic covalent supramolecular motif-guanidine urea structure (GUAs). GUAs contain complex and diverse chemical structures as well as unique bonding characteristics, allowing guanidine urea supramolecular polymers to demonstrate advanced physical properties. Noncovalent interaction aggregates (NIAs) have been confirmed to form in GUA-DCPs through multistage H-bonding and π-π stacking, resulting in an extremely high Young's modulus of 14 GPa, suggesting remarkable mechanical strength. Additionally, guanamine urea linkages in GUAs, a new type of dynamic covalent bond, provide resins with excellent malleability and reprocessability. Guanamine urea metathesis is validated using small molecule model compounds, and the temperature dependent infrared and rheological behavior of GUA-DCPs following the dissociative exchange mechanism. Moreover, the inherent photodynamic antibacterial properties are extensively verified by antibacterial experiments. Even after undergoing three reprocessing cycles, the antibacterial rate of GUA-DCPs remains above 99% after 24 h, highlighting their long-lasting antibacterial effectiveness. GUA-DCPs with dynamic nature, tuneable composition, and unique combination of properties make them promising candidates for various technological advancements.

[Effects of long-term positioning tillage on13C assimilate distribution and grain yield formation in wheat]. / 长期定位耕作模式对小麦13CåŒåŒ–ç‰©åˆ†é å’Œç±½ç²’äº§é‡å½¢æˆçš„å½±å“.

To provide a theoretical basis and technical support for the high-yield and high-efficiency production of wheat, we examined the effects of different tillage patterns on wheat grain yield of Jimai 22 and the physiological mechanisms in an experiment with three treatments: 14 years in rotary tillage (R), minimal and no tillage (S), and minimal and no tillage with a 2-year subsoiling interval (SS). We assessed the light interception by wheat plant canopy, the distribution of photosynthate transport, and grain yield for the three cultivation modes. The results showed that leaf area index was significantly higher for SS treatment than the other treatments at 14-28 days after anthesis. The interception rate and amount of photosynthetically active radiation in the upper and middle layers of wheat canopy were significantly higher for SS treatment than R and S treatments at 21 days after anthesis. The contribution rate of grain assimilation and the distribution proportion of 13C assimilated in grain, and the maximum and average filling rates, were the highest under SS treatment. The 1000-kernel weight for SS treatment increased by 8.7% and 9.6%, and the grain yield increased by 14.2% and 19.4% compared with R and S treatments, respectively. SS treatment significantly improved light energy utilization by wheat canopy, promoted the accumulation and transport of dry matter, increased the grain-filling rate, increased grain weight, which together contributed to the highest grain yield. Therefore, SS was the optimal tillage pattern under the conditions of this experiment.

[Effects of N, P, and K application rates on distribution of 13C assimilates, starch accumulation in grains and fertilizer utilization of wheat]. / 氮磷钾施用量对小麦旗叶13CåŒåŒ–ç‰©åˆ†é ã€ç±½ç²’æ·€ç²‰ç§¯ç´¯å’Œè‚¥æ–™åˆ©ç”¨çš„å½±å“.

Clarifying the appropriate application rates of N, P, and K fertilizers and the physiological mechanisms of wheat under water-saving recharge irrigation in the North China Plain would provide a theoretical basis for formulating reasonable fertilization plans for high-yield and high-efficiency wheat production. We established four treatments with different amounts of nitrogen (N), phosphorus (P2O5), and potassium (K2O) application: 0, 0, and 0 kg·hm-2 (F0), 180, 75, and 60 kg·hm-2 (F1), 225, 120, and 105 kg·hm-2 (F2), and 270, 165, and 150 kg·hm-2 (F3). During the jointing and anthesis stages of wheat, the relative water content of each treatment in the 0-40 cm soil layer was replenished to 70%, to investigate the differences in wheat flag leaf photosynthetic characteristics, distribution of 13C assimilates, grain starch accumulation, and fertilizer utilization. The results showed that the relative chlorophyll content of flag leaves, photosynthetic and chlorophyll fluorescence parameters, 13C assimilate allocation in each organ, enzyme activities involved in starch synthesis, and starch accumulation in the F1 treatment were significantly higher than that in F0 treatment, which was an important physiological basis for the 20.9% increase in grain yield. The above parameters and yield in the F2 and F3 treatments showed no significant increase compared to F1 treatment, while fertilizer productivity and agronomic efficiency of N, P, and K decreased by 17.5%-58.4% and 12.7%-50.7%, respectively. Therefore, F1 could promote flag leaf photosynthetic assimilate production and grain starch accumulation under water-saving supplementary irrigation conditions, resulting in higher grain yield and fertilizer utilization efficiency.

[Effects of phosphorus application rate on distribution of 13C assimilates and spike formation in different til-lers of wheat with supplementary irrigation]. / 补灌条件下施磷量对小麦不同茎蘖13CåŒåŒ–ç‰©åˆ†é åŠå ¶æˆç©—çš„å½±å“.

To clarify the appropriate rate of phosphorus application and physiological mechanism for promoting wheat tillering and efficient utilization of phosphorus fertilizer with supplementary irrigation, we used 'Jimai 22' wheat variety as the test material, to set up three phosphorus application treatments, including low (90 kg P2O5·hm-2, P1), medium (135 kg P2O5·hm-2, P2), and high (180 kg P2O5·hm-2, P3) application rates, with no phosphorus application as the control (P0). We increased the relative soil water content of each treatment at join-ting stage and anthesis stage to 70%, and measured the area of tiller node, the content of endogenous hormones, the number of tillers in each tiller position, photosynthetic parameters, the distribution of 13C assimilates in each stem and tiller, as well as the grain yield and partial productivity of phosphate fertilizer. The results showed that compared with P0 and P1 treatments, P2 significantly increased the area of tiller node and the trans-zeatin (tZ), the photosynthetic parameters of the uppermost expanded leaves of the main stem, the total tillers per plant, and the distribution of 13C assimilates in each tiller. The number of ears per plant was increased by 0.51 and 0.36, and grain yield was increased by 40.3% and 13.2%, respectively. In P3 treatment, the number of tillers increased, but the panicles per plant, and the grain yield and phosphate fertilizer partial productivity decreased. Our results suggested that the moderate phosphorus treatment (135 kg·hm-2) under supplementary irrigation was suitable for high yield and high efficiency of wheat.

Biochar derived from animal and plant facilitates synergistic transformation of heavy metals and phosphorus in sewage sludge composting.

This study investigated the influence of plant-derived biochar (PB) and animal-derived biochar (AB) on behavior of heavy metals and phosphorus fractions during sewage sludge composting. PB was highly effective in reducing the bioavailability of Zn and Cu by 39% and 50%, respectively, while AB decreased the bioavailability of Pb (30%) and Cd (12%). Both biochar increased available phosphorus by over 38%. Acid extractable and bioavailable Pb in AB, and water-soluble, oxidizable and total Zn, acid extractable and oxidizable Cu in PB were positively correlated with moderately resistant organic phosphorus (MROP). Besides, in AB, Cd had strong and positive correlation with highly resistant organic phosphorus (HROP). This suggested biochar facilitated the formation of stable organometallic complexes through binding metal ions to phosphorus fractions, with notable differences based on biochar source. FT-IR showed biochar promoted humification, with PB enhancing carboxyl and polysaccharide formation, while AB encouraged quinone and aryl ether structures. These surface functional groups on the biochar likely contributed to heavy metals and phosphorus binding through chelation, adsorption, and electron shuttling.

SH-Alb inhibits phenotype remodeling of pro-fibrotic macrophage to attenuate liver fibrosis through SIRT3-SOD2 axis.

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment.

Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma.

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.