KIAA0753 enhances osteoblast differentiation suppressed by diabetes.

Diabetes-related bone loss represents a significant complication that persistently jeopardizes the bone health of individuals with diabetes. Primary cilia proteins have been reported to play a vital role in regulating osteoblast differentiation in diabetes-related bone loss. However, the specific contribution of KIAA0753, a primary cilia protein, in bone loss induced by diabetes remains unclear. In this investigation, we elucidated the pivotal role of KIAA0753 as a promoter of osteoblast differentiation in diabetes. RNA sequencing demonstrated a marked downregulation of KIAA0753 expression in pro-bone MC3T3 cells exposed to a high glucose environment. Diabetes mouse models further validated the downregulation of KIAA0753 protein in the femur. Diabetes was observed to inhibit osteoblast differentiation in vitro, evidenced by downregulating the protein expression of OCN, OPN and ALP, decreasing primary cilia biosynthesis, and suppressing the Hedgehog signalling pathway. Knocking down KIAA0753 using shRNA methods was found to shorten primary cilia. Conversely, overexpression KIAA0753 rescued these changes. Additional insights indicated that KIAA0753 effectively restored osteoblast differentiation by directly interacting with SHH, OCN and Gli2, thereby activating the Hedgehog signalling pathway and mitigating the ubiquitination of Gli2 in diabetes. In summary, we report a negative regulatory relationship between KIAA0753 and diabetes-related bone loss. The clarification of KIAA0753's role offers valuable insights into the intricate mechanisms underlying diabetic bone complications.

Growth trends clustering: A novel method for detecting forest disturbances and extracting climate signals in tree rings.

Tree-ring widths contain valuable historical information related to both forest disturbances and climate variability and changes within forests. However, current methods are still unable to accurately distinguish between disturbances and climate signals in tree rings, especially in the case of climate anomalies. To address this issue, we developed a novel method, called Growth Trends Clustering (GTC) that uses the distribution characteristics of tree-ring widths within a stand to distinguish the effects of climate and other forest disturbances. GTC employed a Gaussian mixture model to fit the probability density distribution of annual ring-width index (RWI) in a stand. Discriminative criteria were established to cluster diverse sub-distributions from the Gaussian mixture model into categories of growth release, suppression, or normal trends. This approach allowed us to identify the occurrence, duration, and severity of forest disturbances based on percentage changes in the growth release or suppression categories of trees. And the effect of climate on tree growth was assessed according to the mean statistics of the growth normal categories. Using common forest disturbances such as defoliating insects and thinning as examples, we validated our method using tree-ring collections from six sites in British Columbia and Quebec, Canada. We found that the GTC method was superior to traditional time-series analysis methods (e.g., Radial Growth Averaging, Boundary Line, Absolute Increase, and Curve Intervention Detection) for detecting past forest disturbances and was able to significantly enhance climate signals. In summary, the GTC method presented in this study introduces a novel statistical approach for accurately distinguishing between forest disturbances and climate signals in tree rings. This is particularly important for understanding forest disturbance regimes under climate change and for developing future disturbance mitigation strategies.

Partial asynchrony of coniferous forest carbon sources and sinks at the intra-annual time scale.

As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

Effect of Organic, Nano, and Inorganic Zinc Sources on Growth Performance, Antioxidant Function, and Intestinal Health of Young Broilers.

The study aimed to determine the effects of different zinc sources on growth performance, antioxidant function, and intestinal health of broilers. In total, 240 Ross 308 male broilers with similar weight were randomly assigned to 4 treatments, including zinc sulfate, methionine zinc (Zn-Met), glycine zinc (Zn-Gly), and nano-zinc oxide (ZnO-NPs), with 80 mg zinc/kg diet supplementation. The experiment lasted for 21 days. Results showed dietary supplemental Zn-Gly and Zn-Met increased average daily gain during 1-14 days (P = 0.011), and Zn-Gly, Zn-Met, and ZnO-NP supplementation decreased the ratio of feed to gain during 1-21 days (P = 0.003) compared to zinc sulfate. ZnO-NPs supplementation tended to increase total SOD activity (P = 0.068) and had higher serum IgA content and lower MDA level than the other three groups (P < 0.05). Compared with zinc sulfate, Zn-Met and ZnO-NP supplementation decreased TNF-α mRNA expression (P = 0.048). However, serum biochemical indices, intestinal morphology, and mRNA expressions of tight junction proteins were not affected by different zinc sources (P > 0.05). A differential trend was observed in the beta diversity of bacterial communities among four groups (P = 0.082). The LEfSe analysis showed that bacterial genera Blautia, Ruminococcaceae, Clostridia, Anaerostipes, Eubacterium_ventriosum, Merdibacter, and Oscillospira were enriched in the ZnSO4 group, and the genera Eubacterium_hallii and Anaerotruncus were enriched in the Zn-Gly group. The genera UCG-009 and UCG010 were enriched in ZnO-NPs and Zn-Met groups, respectively. It should be stated dietary supplemental Zn-Met improved growth performance, ZnO-NPs promoted IgA production and reduced occurrences of oxidative stress and inflammation, and different zinc sources enriched different jejunal bacteria genera.

Unearthing New ccr Genes and Staphylococcal Cassette Chromosome Elements in Staphylococci Through Genome Mining.

Staphylococcal cassette chromosome mec (SCCmec) typing is crucial for investigating methicillin-resistant Staphylococcus aureus (MRSA), relying primarily on the combination of ccr and mec gene complexes. To date, 19 ccr genes and 10 ccr gene complexes have been identified, forming 15 SCCmec types. With the vast release of bacterial genome sequences, mining the database for novel ccr gene complexes and SCC/SCCmec elements could enhance MRSA epidemiological studies. In this study, we identified 12 novel ccr genes (6 ccrA, 3 ccrB, and 3 ccrC) through mining of the National Center for Biotechnology Information (NCBI) database, forming 12 novel ccr gene complexes and 10 novel SCC elements. Overexpression of 5 groups of novel Ccr recombinases (CcrA9B3, CcrA10B1, CcrC3, CcrC4, and CcrC5) in a mutant MRSA strain lacking the ccr gene and extrachromosomal circular intermediate (ciSCC) production significantly promoted ciSCC production, demonstrating their biological activity. This discovery provides an opportunity to advance MRSA epidemiological research and develop database-based bacterial typing methods.

Molecular dynamics study on the thermal properties of DGEBA/DETA/Ag/SWCNT-Ag composite materials.

CONTEXT: Traditional conductive adhesives based on epoxy resin system often encounter problems such as high brittleness and low heat resistance. Therefore, it is particularly important to improve the thermal and mechanical properties of the conductive adhesive. In this study, the effects of SWCNT-Ag and SWCNT fillers on the thermal properties of DGEBA/DETA/Ag conductive adhesive system were studied by using molecular dynamics to construct different cross-linking models. The final results show that the addition of SWCNT and SWCNT-Ag can significantly improve the thermal properties of the conductive adhesive. However, the nanosilver particles on the surface of SWCNT-Ag act as a bridge for the connection between SWCNT and Ag in the conductive adhesive. Therefore, SWCNT-Ag has a more positive impact on the thermal properties of DGEBA/DETA/Ag conductive adhesive system. METHODS: In this paper, the influence of SWCNT-Ag on the thermal properties of traditional DGEBA/DETA/Ag conductive adhesive system was studied by using Materials Studio software. The volume shrinkage, glass transition temperature, thermal expansion coefficient, and thermal conductivity of the material were calculated based on COMPASS force field. The thermal conductivity is calculated by using reverse non-equilibrium molecular dynamics method. Finally, it is found that SWCNT-Ag has a positive effect on the thermal properties of the conductive adhesive system by comparing several groups of calculation data.

Landscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila.

Gut Akkermansia muciniphila (Akk) has been implicated in impacting immunotherapy or oncogenesis. This study aims to dissect the Akk-associated tumor immune ecosystem (TIME) by single-cell profiling coupled with T cell receptor (TCR) sequencing. We adopted mouse cancer models under anti-PD-1 immunotherapy, combined with oral administration of three forms of Akk, including live Akk, pasteurized Akk (Akk-past), or its membrane protein Amuc_1100 (Amuc). We show that live Akk is most effective in activation of CD8 T cells by rescuing the exhausted type into cytotoxic subpopulations. Remarkably, only live Akk activates MHC-II-pDC pathways, downregulates CXCL3 in Bgn(+)Dcn(+) cancer-associated fibroblasts (CAFs), blunts crosstalk between Bgn(+)Dcn(+) CAFs and PD-L1(+) neutrophils by a CXCL3-PD-L1 axis, and further suppresses the crosstalk between PD-L1(+) neutrophils and CD8 T cells, leading to the rescue of exhausted CD8 T cells. Together, this comprehensive picture of the tumor ecosystem provides deeper insights into immune mechanisms associated with gut Akk-dependent anti-PD-1 immunotherapy.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.

Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.

The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.

Interguild fungal competition in litter and soil inversely modulate microbial necromass accumulation during Loess Plateau forest succession.

Microbial interactions determine ecosystem carbon (C) and nutrient cycling, yet it remains unclear how interguild fungal interactions modulate microbial residue contribution to soil C pools (SOC) during forest succession. Here, we present a region-wide investigation of the relative dominance of saprophytic versus symbiotic fungi in litter and soil compartments, exploring their linkages to soil microbial residue pools and potential drivers along a chronosequence of secondary Chinese pine (Pinus tabulaeformis) forests on the Loess Plateau. Despite minor changes in C and nitrogen (N) stocks in the litter or soil layers across successional stages, we found significantly lower soil phosphorus (P) stocks, higher ratios of soil C: N, soil N: P and soil C: P but lower ratios of litter C: N and litter C: P in old (>75 years) than young stands (<30 years). Pine stand development altered the saprotroph: symbiotroph ratios of fungal communities to favor the soil symbiotrophs versus the litter saprotrophs. The dominance of saprotrophs in litter is positively related to microbial necromass contribution to SOC, which is negatively related to the dominance of symbiotrophs in soils. Antagonistic interguild fungal competition in litter and soil layers, in conjunction with increased fungal but decreased bacterial necromass contribution to SOC, jointly contribute to unchanged total necromass contribution to SOC with stand development. The saprotroph: symbiotroph ratios in litter and soil layers are mainly driven by soil P stocks and stand parameters (e.g., stand age and slope), respectively, while substrate stoichiometries primarily regulate microbial necromass accumulation and fungal: bacterial necromass ratios. These results provide novel insights into how microbial interactions at local spatial scales modulate temporal changes in SOC pools, with management implications for mitigating regional land degradation.

Lignin-Based Mesoporous Hollow Carbon@MnO2 Nanosphere Composite as an Anodic Material for Lithium-Ion Batteries.

The lignin-based mesoporous hollow carbon@MnO2 nanosphere composites (L-C-NSs@MnO2) were fabricated by using lignosulfonate as the carbon source. The nanostructured MnO2 particles with a diameter of 10~20 nm were uniformly coated onto the surfaces of the hollow carbon nanospheres. The obtained L-C-NSs@MnO2 nanosphere composite showed a prolonged cycling lifespan and excellent rate performance when utilized as an anode for LIBs. The L-C-NSs@MnO2 nanocomposite (24.6 wt% of MnO2) showed a specific discharge capacity of 478 mAh g-1 after 500 discharge/charge cycles, and the capacity contribution of MnO2 in the L-C-NSs@MnO2 nanocomposite was estimated ca. 1268.8 mAh g-1, corresponding to 103.2% of the theoretical capacity of MnO2 (1230 mAh g-1). Moreover, the capacity degradation rate was ca. 0.026% per cycle after long-term and high-rate Li+ insertion/extraction processes. The three-dimensional lignin-based carbon nanospheres played a crucial part in buffering the volumetric expansion and agglomeration of MnO2 nanoparticles during the discharge/charge processes. Furthermore, the large specific surface areas and mesoporous structure properties of the hollow carbon nanospheres significantly facilitate the fast transport of the lithium-ion and electrons, improving the electrochemical activities of the L-C-NSs@MnO2 electrodes. The presented work shows that the combination of specific structured lignin-based carbon nanoarchitecture with MnO2 provides a brand-new thought for the designation and synthesis of high-performance materials for energy-related applications.

Bibliometric and visual analyses of trends in the field of T cell exhaustion research: Findings from 2000 to 2022.

BACKGROUND: T cell exhaustion refers to a state wherein T cells become less functional as a result of their prolonged exposure to cognate antigens. A wealth of T cell exhaustion-focused research has been conducted in recent decades, transforming the current understanding of this biologically relevant process. However, there have not been any comprehensive bibliometric analyses to date focused on clarifying the T cell exhaustion-related research landscape. Here, a bibliometric analysis was thus conducted with the goal of better elucidating the current state of knowledge and emerging research hotspots in this field. METHODS: The Web of Science Core Collection was searched for articles and reviews related to T cell exhaustion, with the CiteSpace and VOSviewer programs then being employed to analyze the countries, institutions, authors, references, and keywords associated with studies in this research space. RESULTS: In total, 2676 studies were incorporated in this analysis, highlighting progressive annual increases in the number of T cell exhaustion-focused publications over the study period. These publications were affiliated with 3117 institutions in 85 countries, with the USA and China being the largest contributors to the field. Of the 18,032 authors associated with these publications, E. John Wherry exhibited the highest publication count and the greatest citation frequency. Keyword analyses indicated that immunotherapy, T cell exhaustion, and PD-1 are the dominant foci for T cell exhaustion-related research. CONCLUSION: These findings highlight the importance of collaborations among institutions and nations in order to further propel novel studies of T cell exhaustion. Efforts to unravel the signal transduction and transcriptional mechanisms underlying the onset of T cell exhaustion were also identified as an emerging hotspot in this field. Ultimately, these results support the pivotal status of T cell exhaustion research as a key direction for immunotherapeutic research and development efforts in the coming years.

Temporary Knockdown of p53 During Focal Limb Irradiation Increases the Development of Sarcomas.

Approximately half of patients with cancer receive radiotherapy and, as cancer survivorship increases, the low rate of radiation-associated sarcomas is rising. Pharmacologic inhibition of p53 has been proposed as an approach to ameliorate acute injury of normal tissues from genotoxic therapies, but how this might impact the risk of therapy-induced cancer and normal tissue injuries remains unclear. We utilized mice that express a doxycycline (dox)-inducible p53 short hairpin RNA to reduce Trp53 expression temporarily during irradiation. Mice were placed on a dox diet 10 days prior to receiving 30 or 40 Gy hind limb irradiation in a single fraction and then returned to normal chow. Mice were examined weekly for sarcoma development and scored for radiation-induced normal tissue injuries. Radiation-induced sarcomas were subjected to RNA sequencing. Following single high-dose irradiation, 21% of animals with temporary p53 knockdown during irradiation developed a sarcoma in the radiation field compared with 2% of control animals. Following high-dose irradiation, p53 knockdown preserves muscle stem cells, and increases sarcoma development. Mice with severe acute radiation-induced injuries exhibit an increased risk of developing late persistent wounds, which were associated with sarcomagenesis. RNA sequencing revealed radiation-induced sarcomas upregulate genes related to translation, epithelial-mesenchymal transition (EMT), inflammation, and the cell cycle. Comparison of the transcriptomes of human and mouse sarcomas that arose in irradiated tissues revealed regulation of common gene programs, including elevated EMT pathway gene expression. These results suggest that blocking p53 during radiotherapy could minimize acute toxicity while exacerbating late effects including second cancers. SIGNIFICANCE: Strategies to prevent or mitigate acute radiation toxicities include pharmacologic inhibition of p53 and other cell death pathways. Our data show that temporarily reducing p53 during irradiation increases late effects including sarcomagenesis.

VS-Cambium-Developer: A New Predictive Model of Cambium Functioning under the Influence of Environmental Factors.

Climate changes influence seasonal tree-ring formation. The result is a specific cell structure dependent on internal processes and external environmental factors. One way to investigate and analyze these relationships is to apply diverse simulation models of tree-ring growth. Here, we have proposed a new version of the VS-Cambium-Developer model (VS-CD model), which simulates the cambial activity process in conifers. The VS-CD model does not require the manual year-to-year calibration of parameters over a long-term cell production reconstruction or forecast. Instead, it estimates cell production and simulates the dynamics of radial cell development within the growing seasons. Thus, a new software based on R programming technology, able to efficiently adapt to the VS model online platform, has been developed. The model was tested on indirect observations of the cambium functioning in Larix sibirica trees from southern Siberia, namely on the measured annual cell production from 1963 to 2011. The VS-CD model proves to simulate cell production accurately. The results highlighted the efficiency of the presented model and contributed to filling the gap in the simulations of cambial activity, which is critical to predicting the potential impacts of changing environmental conditions on tree growth.

Acceleration of Photocatalytic CO2 Reduction at Intimate Interface in AgBr/BiOBr Heterojunctions via a Co-anion Strategy.

Constructing heterojunctions with strong interfacial interactions can accelerate the transfer and separation of photogenerated charge carriers. However, finding a simple strategy to construct tightly connected heterojunctions remains a major challenge. In this work, AgBr/BiOBr S-scheme heterojunctions were designed via a straightforward co-anionic strategy without using a solvent. The experimental results indicate that the AgBr/BiOBr heterojunction with a close contact interface can extend the use of visible light, accelerate the separation, and induce the transfer of photoelectrons and holes while maintaining an excellent redox capacity. Undoubtedly, the photocatalytic reduction rate of carbon dioxide to carbon monoxide by 1.0 AgBr/BiOBr is 87.73 µmol·g-1·h-1 (quantum efficiency is 0.57%), which is 12.15 times and 4.45 times higher than that of pure AgBr and BiOBr, respectively. The present work provides insights into a simple strategy for the preparation of strongly interacting interfacial heterojunctions for photocatalytic CO2 reduction.

Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.

Mismatch between primary and secondary growth and its consequences on wood formation in Qinghai spruce.

The connections between the primary and secondary growth of trees allows better understanding of the dynamics of carbon sequestration in forest ecosystems. The relationship between primary and secondary growth of trees could change due to the diverging responses of meristems to climate warming. In this study, the bud phenology and radial growth dynamics of Qinghai spruce (Picea crassifolia) in arid and semi-arid areas of China in 2019 and 2020 were weekly monitored to analyze their response to different weather conditions and their links with carbon sink. Xylem anatomical traits (i.e. lumen radial diameter and cell wall thickness) were quantified along cell radial files after the end of xylem lignification to calculate the early-to-latewood transition date. Winter and early spring (January-March) were warmer in 2020 with a colder April compared with 2019. Precipitation in April-June was lower in 2020 than in 2019. In 2019, bud phenology occurred earlier, while the onset of xylem formation and the early-to-latewood transition date were delayed. The duration from the beginning of split bud and exposed shoot to the early-to-latewood transition date was positively correlated with the radial width of earlywood (accounting for ~80% of xylem width) and total xylem width. The longer duration of xylem cell division did not increase xylem cell production and radial width. Moreover, the duration from bud burst to the early-to-latewood transition date in 2020 was negatively linked with early phloem cell production as compared with 2019. Our findings suggest that warm conditions in winter and early spring promote the xylogenesis of Qinghai spruce, but might delay bud burst. However, the xylem width increments largely depend on the duration from bud burst to the start of latewood cell division rather than on the earlier xylogenesis and longer duration of xylem cell differentiation induced by warm conditions.

Liquid nitrogen frozen cells for chemotherapy drug delivery and vaccination of melanoma.

PURPOSE: Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging. METHODS: Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover,  the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated. RESULTS: The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4+ and CD8+ T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8+ T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group. CONCLUSION: In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.

Precipitation regulates the responses of xylem phenology of two dominant tree species to temperature in arid and semi-arid forest of the southern Altai Mountains.

Arid and semi-arid forests are important carbon sinks, with implications for the global carbon balance. However, the impacts of climate warming on the growth of arid and semi-arid forest tree species and ecosystem carbon sink dynamics remain uncertain because the effects of the complex interactions between precipitation and temperature on xylem phenology are not clearly understood. Here, we monitored xylem formation over two years in two dominant tree species (Siberian larch, Larix sibirica Ledeb.; Siberian spruce, Picea obovata Ledeb.) along the arid and semi-arid southern Altai Mountains of Central Asia. We determined that temperature interaction with precipitation plays a key role in regulating xylem phenology of these two species, with differences between species. Under rising mean annual temperatures, the growth of L. sibirica advanced as the onset of xylem formation was not limited by early season water availability. However, the earlier cessation of cell enlargement, likely due to legacy effects, compensated for such advancement. In contrast, water stress constrained the advancement of xylem formation under rising temperatures in P. obovata. Nevertheless, water stress was seemingly relieved later in the growing season and consequently did not lead to the earlier cessation of xylem formation. Our results demonstrate that precipitation drives species-specific response to rising temperatures and thus is a key driver of growing season length and carbon sink dynamics in arid and semi-arid forests under climate warming. Integrating the effects of temperature and precipitation on xylem phenology in climate models may improve estimates of climate-carbon feedback in arid and semi-arid forests under future warming scenarios.