Unconventional tonicity-regulated nuclear trafficking of NFAT5 mediated by KPNB1, XPOT and RUVBL2.

NFAT5 is the only known mammalian tonicity-responsive transcription factor with an essential role in cellular adaptation to hypertonic stress. It is also implicated in diverse physiological and pathological processes. NFAT5 activity is tightly regulated by extracellular tonicity, but the underlying mechanisms remain elusive. Here, we demonstrate that NFAT5 enters the nucleus via the nuclear pore complex. We found that NFAT5 utilizes a unique nuclear localization signal (NFAT5-NLS) for nuclear import. siRNA screening revealed that only karyopherin ß1 (KPNB1), but not karyopherin α, is responsible for the nuclear import of NFAT5 via direct interaction with the NFAT5-NLS. Proteomics analysis and siRNA screening further revealed that nuclear export of NFAT5 under hypotonicity is driven by exportin-T (XPOT), where the process requires RuvB-like AAA-type ATPase 2 (RUVBL2) as an indispensable chaperone. Our findings have identified an unconventional tonicity-dependent nucleocytoplasmic trafficking pathway for NFAT5 that represents a critical step in orchestrating rapid cellular adaptation to change in extracellular tonicity. These findings offer an opportunity for the development of novel NFAT5 targeting strategies that are potentially useful for the treatment of diseases associated with NFAT5 dysregulation.

China's wetland soil organic carbon pool: New estimation on pool size, change, and trajectory.

Robust estimates of wetland soil organic carbon (SOC) pools are critical to understanding wetland carbon dynamics in the global carbon cycle. However, previous estimates were highly variable and uncertain, due likely to the data sources and method used. Here we used machine learning method to estimate SOC storage and their changes over time in China's wetlands based on wetland SOC density database, associated geospatial environmental data, and recently published wetland maps. We built a database of wetland SOC density in China that contains 809 samples from 181 published studies collected over the last 20 years as presented in the published literature. All samples were extended and standardized to a 1-m depth, on the basis of the relationship between SOC density data from soil profiles of different depths. We used three different machine learning methods to evaluate their robustness in estimating wetland SOC storage and changes in China. The results indicated that random forest model achieved accurate wetland SOC estimation with R2 being .65. The results showed that average SOC density of top 1 m in China's wetlands was 25.03 ± 3.11 kg C m-2 in 2000 and 26.57 ± 3.73 kg C m-2 in 2020, an increase of 6.15%. SOC storage change from 4.73 ± 0.58 Pg in 2000 to 4.35 ± 0.61 Pg in 2020, a decrease of 8.03%, due to 13.6% decreased in wetland area from 189.12 × 103 to 162.8 × 103 km2 in 2020, despite the increase in SOC density during the same time period. The carbon accumulation rate was 107.5 ± 12.4 g C m-2 year-1 since 2000 in wetlands with no area changes. Climate change caused variations in wetland SOC density, and a future warming and drying climate would lead to decreases in wetland SOC storage. Estimates under Shared Socioeconomic Pathway 1-2.6 (low-carbon emissions) suggested that wetland SOC storage in China would not change significantly by 2100, but under Shared Socioeconomic Pathway 5-8.5 (high-carbon emissions), it would decrease significantly by approximately 5.77%. In this study, estimates of wetland SOC storage were optimized from three aspects, including sample database, wetland extent, and estimation method. Our study indicates the importance of using consistent SOC density and extent data in estimating and projecting wetland SOC storage.

Gastrointestinal perforation associated with novel antineoplastic agents: A real-world study based on the FDA Adverse Event Reporting System.

Purpose: Gastrointestinal perforation (GIP) is a fatal adverse event (AE). The AE of GIP induced by novel antineoplastic agents has attracted attention recently. We aimed to explore the AE signals of GIP related to novel antineoplastic agents comprehensively based on the FDA Adverse Event Reporting System (FAERS). Methods: The FAERS database containing 71 quarters of records was used for analysis. Reporting odds ratio (ROR), information component (IC), and empirical Bayesian geometric mean (EBGM) were utilized to evaluate the signals of GIP associated with novel antineoplastic drugs. Standardization of drug names was by employing MedEx-UIMA software and Python. Data analysis and visualization were performed using MySQL Workbench and R software. Results: After cleaning and handling the data, 5226 GIP cases were identified that were associated with new antineoplastic medications, where these agents were the main suspected contributors. A total of 37 novel antineoplastic drugs were detected with signals of GIP for ROR and IC. Only 22 drugs showed statistically significant signals for EBGM. We found the GIP signals of 22 novel antineoplastic drugs overlapped for the 3 indicators, including anti-vascular endothelial growth factor/vascular endothelial growth factor receptor, anti-endothelial growth factor receptor, immune checkpoint inhibitors, and so on. Conclusion: The potential risk of GIP associated with several novel antineoplastic agents was identified through data mining, which provided valuable information on the safety risks associated with GIP among these drugs. The potential threat of GIP should be recognized and managed properly when using these novel antineoplastic agents.

Large stocks of peatland carbon and nitrogen are vulnerable to permafrost thaw.

Northern peatlands have accumulated large stocks of organic carbon (C) and nitrogen (N), but their spatial distribution and vulnerability to climate warming remain uncertain. Here, we used machine-learning techniques with extensive peat core data (n > 7,000) to create observation-based maps of northern peatland C and N stocks, and to assess their response to warming and permafrost thaw. We estimate that northern peatlands cover 3.7 ± 0.5 million km2 and store 415 ± 150 Pg C and 10 ± 7 Pg N. Nearly half of the peatland area and peat C stocks are permafrost affected. Using modeled global warming stabilization scenarios (from 1.5 to 6 °C warming), we project that the current sink of atmospheric C (0.10 ± 0.02 Pg C⋅y-1) in northern peatlands will shift to a C source as 0.8 to 1.9 million km2 of permafrost-affected peatlands thaw. The projected thaw would cause peatland greenhouse gas emissions equal to ∼1% of anthropogenic radiative forcing in this century. The main forcing is from methane emissions (0.7 to 3 Pg cumulative CH4-C) with smaller carbon dioxide forcing (1 to 2 Pg CO2-C) and minor nitrous oxide losses. We project that initial CO2-C losses reverse after ∼200 y, as warming strengthens peatland C-sinks. We project substantial, but highly uncertain, additional losses of peat into fluvial systems of 10 to 30 Pg C and 0.4 to 0.9 Pg N. The combined gaseous and fluvial peatland C loss estimated here adds 30 to 50% onto previous estimates of permafrost-thaw C losses, with southern permafrost regions being the most vulnerable.

Comprehensive genomic analysis of primary malignant melanoma of the esophagus reveals similar genetic patterns compared with epithelium-associated melanomas.

Primary malignant melanoma of the esophagus (PMME) is an exceedingly rare disease with a poor prognosis. The etiology of PMME remains largely unknown and genetic characteristics are yet to be clarified, essential for identifying potential therapeutic targets and defining treatment guidelines. Here, we performed whole-exome sequencing on 47 formalin-fixed paraffin-embedded specimens from 18 patients with PMME, including 23 tumor samples, 6 metastatic lymph nodes, and 18 tumor-adjacent normal tissues. The genomic features of PMME were comprehensively characterized, and comparative genomic analysis was further performed between these specimens and 398 skin cutaneous melanomas (SKCM), 67 non-esophagus mucosal melanomas (NEMM), and 79 uveal melanomas (UVM). In the PMME cohort, recurrently mutated driver genes, such as MUC16, RANBP2, NRAS, TP53, PTPRT, NF1, MUC4, KMT2C, and BRAF, were identified. All RANBP2 mutations were putatively deleterious, and most affected samples had multipoint mutations. Furthermore, RANBP2 showed parallel evolution by multiregional analysis. Whole-genome doubling was an early truncal event that occurred before most driver mutations, except for in TP53. An ultraviolet radiation-related mutational signature, SBS38, was identified as specific to epithelial melanomas and could predict inferior survival outcomes in both PMME and SKCM patients. Comparing the mutational and copy number landscapes between PMME and other subtypes of melanoma revealed that PMME has a similar genomic pattern and biological characteristics to SKCM. In summary, we comprehensively defined the key genomic aberrations and mutational processes driving PMME and suggested for the first time that PMME may share similar genomic patterns with SKCM; therefore, patients with rare melanomas, such as PMME, may benefit from the current treatment used for common cutaneous melanoma.

Torsade de Pointes/QT Prolongation Associated with Antifungal Triazoles: A Pharmacovigilance Study Based on the U.S. FDA Adverse Event Reporting System（FAERS）.

PURPOSE: Torsade de pointes (TdP)/QT prolongation is a fatal adverse event (AE) when using antifungal triazoles. We aimed to compare the AE signals of TdP/QT prolongation and onset time among different drugs of this kind comprehensively. METHODS: This retrospective research was to analyze the U.S. FDA Adverse Event Reporting System (FAERS) database containing 71 quarters of reports through online retrieval. We calculated the strength of signals of TdP/QT prolongation related to 4 drugs of triazoles by using the following indicators: reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). The onset time to the AE of TdP/QT prolongation among different antifungal triazoles were compared by using nonparametric tests. Management and visualization of the data were performed by employing MySQL Workbench and R software. The data information including clinical features, AE onset time, and outcomes were extracted for analysis as well. RESULTS: After filtering the FAERS database, 448 reports were identified that were associated with TdP/QT prolongation when 4 triazoles played the primary suspected role.  The AE signals of TdP/QT prolongation for any involved antifungal triazoles were detected by using the 4 detection indicators, and the signals of fluconazole are the strongest. This AE mostly occurred within 0-14 days after triazoles therapy. CONCLUSIONS: The AE signals of TdP/QT prolongation associated with antifungal triazoles were very intense. Attention must be paid to the TdP/QT prolongation of various triazoles, particularly at the early stages of antifungal triazoles treatment.

Widespread global peatland establishment and persistence over the last 130,000 y.

Glacial-interglacial variations in CO2 and methane in polar ice cores have been attributed, in part, to changes in global wetland extent, but the wetland distribution before the Last Glacial Maximum (LGM, 21 ka to 18 ka) remains virtually unknown. We present a study of global peatland extent and carbon (C) stocks through the last glacial cycle (130 ka to present) using a newly compiled database of 1,063 detailed stratigraphic records of peat deposits buried by mineral sediments, as well as a global peatland model. Quantitative agreement between modeling and observations shows extensive peat accumulation before the LGM in northern latitudes (>40°N), particularly during warmer periods including the last interglacial (130 ka to 116 ka, MIS 5e) and the interstadial (57 ka to 29 ka, MIS 3). During cooling periods of glacial advance and permafrost formation, the burial of northern peatlands by glaciers and mineral sediments decreased active peatland extent, thickness, and modeled C stocks by 70 to 90% from warmer times. Tropical peatland extent and C stocks show little temporal variation throughout the study period. While the increased burial of northern peats was correlated with cooling periods, the burial of tropical peat was predominately driven by changes in sea level and regional hydrology. Peat burial by mineral sediments represents a mechanism for long-term terrestrial C storage in the Earth system. These results show that northern peatlands accumulate significant C stocks during warmer times, indicating their potential for C sequestration during the warming Anthropocene.

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse. METHODS: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. RESULTS: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse. CONCLUSIONS: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.

Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors.

Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. Nevertheless, the successful application of TIL therapy currently is still limited to several types of tumors. Herein in this review, we summarize the fundamental work in the field of TIL therapy and the current landscape and advances of TIL clinical trials worldwide. Moreover, the limitations of the current TIL regimen have been discussed and the opportunities and challenges in the development of next-generation TIL are highlighted. Finally, the future directions of TIL therapy towards a broader clinical application have been proposed.

Anthropogenic disturbances caused declines in the wetland area and carbon pool in China during the last four decades.

Wetlands are among the natural ecosystems with the highest soil carbon stocks on Earth. However, how anthropogenic disturbances have impacted the quantity and distribution of wetland carbon pool in China is not well understood. Here we used a comprehensive countrywide wetland inventory and Landsat 8 data to document the spatial patterns in China's wetland areas and carbon pools and to understand the underlying causes of their changes from the 1980s to 2010s. We found that the wetland area and carbon pool have decreased from 4.11 × 105  km2 and 15.2 Pg C in the 1980s to 2.14 × 105  km2 and 7.6 Pg C in the 2010s, respectively. Using the human influence index (HII) as a quantitative measure of anthropogenic disturbance intensity, we found a positive relationship between the HII values and wetland decreases in many regions and across China as a whole-which have increased 17% during the time period-indicating that anthropogenic disturbances have been a major factor causing wetland destruction in recent decades. This study provides new evidence for recent changes in China's wetland carbon pool and emphasizes the importance of mitigating anthropogenic disturbances for wetland conservation.

Reconciling carbon-cycle processes from ecosystem to global scales.

Understanding carbon (C) dynamics from ecosystem to global scales remains a challenge. Although expansion of global carbon dioxide (CO2) observatories makes it possible to estimate C-cycle processes from ecosystem to global scales, these estimates do not necessarily agree. At the continental US scale, only 5% of C fixed through photosynthesis remains as net ecosystem exchange (NEE), but ecosystem measurements indicate that only 2% of fixed C remains in grasslands, whereas as much as 30% remains in needleleaf forests. The wet and warm Southeast has the highest gross primary productivity and the relatively wet and cool Midwest has the highest NEE, indicating important spatial mismatches. Newly available satellite and atmospheric data can be combined in innovative ways to identify potential C loss pathways to reconcile these spatial mismatches. Independent datasets compiled from terrestrial and aquatic environments can now be combined to advance C-cycle science across the land-water interface.

Holocene peatland and ice-core data constraints on the timing and magnitude of CO2 emissions from past land use.

CO2 emissions from preindustrial land-use change (LUC) are subject to large uncertainties. Although atmospheric CO2 records suggest only a small land carbon (C) source since 5,000 y before present (5 kyBP), the concurrent C sink by peat buildup could mask large early LUC emissions. Here, we combine updated continuous peat C reconstructions with the land C balance inferred from double deconvolution analyses of atmospheric CO2 and [Formula: see text]C at different temporal scales to investigate the terrestrial C budget of the Holocene and the last millennium and constrain LUC emissions. LUC emissions are estimated with transient model simulations for diverging published scenarios of LU area change and shifting cultivation. Our results reveal a large terrestrial nonpeatland C source after the Mid-Holocene (66 [Formula: see text] 25 PgC at 7-5 kyBP and 115 [Formula: see text] 27 PgC at 5-3 kyBP). Despite high simulated per-capita CO2 emissions from LUC in early phases of agricultural development, humans emerge as a driver with dominant global C cycle impacts only in the most recent three millennia. Sole anthropogenic causes for particular variations in the CO2 record ([Formula: see text]20 ppm rise after 7 kyBP and [Formula: see text]10 ppm fall between 1500 CE and 1600 CE) are not supported. This analysis puts a strong constraint on preindustrial vs. industrial-era LUC emissions and suggests that upper-end scenarios for the extent of agricultural expansion before 1850 CE are not compatible with the C budget thereafter.

Population pharmacokinetics and Bayesian estimation of mycophenolic acid concentrations in Chinese adult renal transplant recipients.

Mycophenolate mofetil (MMF) is an important immunosuppressant used in renal transplantation, and mycophenolic acid (MPA) is the active component released from the ester prodrug MMF. The objective of this study was to investigate the population pharmacokinetics of mycophenolic acid (MPA) following oral administration of MMF in Chinese adult renal transplant recipients and to identify factors that explain MPA pharmacokinetic variability. Pharmacokinetic data for MPA and covariate information were retrospectively collected from 118 patients (79 patients were assigned to the group for building the population pharmacokinetic model, while 39 patients were assigned to the validation group). Population pharmacokinetic data analysis was performed using the NONMEM software. The pharmacokinetics of MPA was best described by a two-compartment model with a first-order absorption rate with no lag time. Body weight and serum creatinine level were positively correlated with apparent clearance (CL/F). The polymorphism in uridine diphosphate glucuronosyltransferase gene, UGT2B7, significantly explained the interindividual variability in the initial volume of distribution (V1/F). The estimated population parameters (and interindividual variability) were CL/F 18.3 L/h (34.2%) and V1/F 27.9 L (21.3%). The interoccasion variability was 13.7%. These population pharmacokinetic data have significant clinical value for the individualization of MMF therapy in Chinese adult renal transplant patients.

Probing cigarette smoke-induced DNA single-strand breaks and screening natural protective compounds by use of magnetic bead-based chemiluminescence.

Magnetic bead (MB)-based chemiluminescence (CL) ELISA can be a sample-thrifty, time-saving tool for evaluation of cigarette smoke-induced DNA single-strand breaks (SSBs) with high specificity. This article describes a novel approach using immobilized oligonucleotide on MBs to determine cigarette smoke-induced DNA SSBs and screen some protective natural compounds. Typically, fluorescein-labeled DNA (FAM-DNA) was immobilized on the MBs and then oxidized by the smoke in the absence or presence of natural compounds, and a part of FAM-DNA was fragmented due to cigarette smoke-induced DNA SSB and then detached from MBs whereas other non-broken FAM-DNA still remained on MBs. Then, any broken FAM-DNA fragments, complex tobacco smoke matrix, and other stuff related with natural compounds were conveniently washed away by a magnetic force, and thus possible interfering substances were completely removed. Finally, those remaining non-broken FAM-DNA on MBs were reacted with HRP-labeled anti-fluorescein antibody and then detected by CL ELISA. CL signal was converted to molar concentrations of the FAM-DNA by interpolation from a pre-determined standard linear calibration curve. The level of DNA SSBs induced by cigarette smoke was thus calculated using the method. A library of 30 natural products was subsequently screened, and two among them were found to protect DNA from oxidative damage and thus may be promising compounds for the development of new drugs. The method developed will be useful for quantitative screening of drug genotoxicity in terms of induction of DNA SSBs. Graphical abstract ᅟ.

Carbon accumulation and sequestration of lakes in China during the Holocene.

Understanding the responses of lake systems to past climate change and human activity is critical for assessing and predicting the fate of lake carbon (C) in the future. In this study, we synthesized records of the sediment accumulation from 82 lakes and of C sequestration from 58 lakes with direct organic C measurements throughout China. We also identified the controlling factors of the long-term sediment and C accumulation dynamics in these lakes during the past 12 ka (1 ka = 1000 cal yr BP). Our results indicated an overall increasing trend of sediment and C accumulation since 12 ka, with an accumulation peak in the last couple of millennia for lakes in China, corresponding to terrestrial organic matter input due to land-use change. The Holocene lake sediment accumulation rate (SAR) and C accumulation rate (CAR) averaged (mean ± SE) 0.47 ± 0.05 mm yr(-1) and 7.7 ± 1.4 g C m(-2)  yr(-1) in China, respectively, comparable to the previous estimates for boreal and temperate regions. The SAR for lakes in the East Plain of subtropical China (1.05 ± 0.28 mm yr(-1) ) was higher than those in other regions (P < 0.05). However, CAR did not vary significantly among regions. Overall, the variability and history of climate and anthropogenic interference regulated the temporal and spatial dynamics of sediment and C sequestration for lakes in China. We estimated the total amount of C burial in lakes of China as 8.0 ± 1.0 Pg C. This first estimation of total C storage and dynamics in lakes of China confirms the importance of lakes in land C budget in monsoon-influenced regions.

Rapid deglacial and early Holocene expansion of peatlands in Alaska.

Northern peatlands represent one of the largest biospheric carbon (C) reservoirs; however, the role of peatlands in the global carbon cycle remains intensely debated, owing in part to the paucity of detailed regional datasets and the complexity of the role of climate, ecosystem processes, and environmental factors in controlling peatland C dynamics. Here we used detailed C accumulation data from four peatlands and a compilation of peatland initiation ages across Alaska to examine Holocene peatland dynamics and climate sensitivity. We find that 75% of dated peatlands in Alaska initiated before 8,600 years ago and that early Holocene C accumulation rates were four times higher than the rest of the Holocene. Similar rapid peatland expansion occurred in West Siberia during the Holocene thermal maximum (HTM). Our results suggest that high summer temperature and strong seasonality during the HTM in Alaska might have played a major role in causing the highest rates of C accumulation and peatland expansion. The rapid peatland expansion and C accumulation in these vast regions contributed significantly to the peak of atmospheric methane concentrations in the early Holocene. Furthermore, we find that Alaskan peatlands began expanding much earlier than peatlands in other regions, indicating an important contribution of these peatlands to the pre-Holocene increase in atmospheric methane concentrations.

Topographic and climatic controls of peatland distribution on the Tibetan Plateau.

The Tibetan Plateau (TP) hosts a variety of mountain peatlands that are sensitive to the amplified warming in this region. However, we still lack a basic understanding of environmental and climatic factors controlling peatland distribution in the region. Here we use a bioclimatic envelope model (PeatStash) and environmental analysis that utilise three peatland datasets-(a) the well-studied Zoige peatland complex, (b) a literature-based dataset of TP peatlands sites, and (c) an existing global peatland map (PEATMAP)-to investigate major drivers of peatland distribution in the TP. The Zoige peatland complex is defined by gentle slopes (< 2°), mean annual temperature at 0-2 °C, and soil moisture index > 1.7, much narrower thresholds than those stemming from PEATMAP. Using these narrower thresholds to predict future changes, we found that the Zoige peatland complex will shrink greatly under full-range future warming scenarios (both SSP1-2.6 and SSP5-8.5). Modelling peatland distribution in the entire TP remains challenging because accurate environmental and climate data at high resolution and a reliable peatland distribution map are still lacking. Improved peatland mapping supported by ground-truthing is necessary to understand drivers of peatland distribution, assess carbon storage and other ecosystem services, and predict the TP's peatlands fate under climate change.

Resveratrol-Loaded Dipalmitoylphosphatidylcholine Liposomal Large Porous Microparticle Inhalations for the Treatment of Bacterial Pneumonia Caused by Acinetobacter baumannii.

Background: Acinetobacter baumannii-mediated bacterial pneumonia is a common disease that is harmful to human health. Dipalmitoylphosphatidylcholine (DPPC) is the major lipid component of the pulmonary surfactant (PS) found in the alveolar space; the PS helps to keep surface tension low, which allows for improved oxygen delivery. Resveratrol (RE) is a phytoalexin found in plants that is released in response to injury or infection. The therapeutic effect of Re is limited due to its low solubility and bioavailability. In this study, we report pulmonary delivery of Re-loaded DPPC liposomal large porous microparticles (RDLPMs) for treatment of A. baumannii-induced pneumonia. Methods: Novel RDLPMs were prepared by rotary evaporation and a freeze-drying method in this study. RDLPMs were evaluated by the particle size, electric potential, in vitro release, and particle size distribution. A rat model of A. baumannii-mediated pneumonia was established and used for pharmacodynamic evaluations. Results: The Re-loaded DPPC liposomes (RDLs) consisted of Re/DPPC (1:3, mol/mol) and DPPC/cholesterol (3:1, w/w), with a hydration time of 15 minutes. The RDLs had a high encapsulation efficiency of 69.8% ± 1.6%, a mean size of 191.5 ± 4.5 nm, and a high zeta potential of 12.4 ± 1.5 mV. The RDLPMs were composed of mannitol/large porous microparticles/RDLs (1:4:2, w/w/w) and had a loading efficiency of 2.20% ± 0.24%. The RDLPMs had an aerodynamic diameter (2.73 ± 0.65 µm), a good fluidity (28.30° ± 6.13°), and demonstrated high lung deposition (fine particle fraction = 43.33%). Surprisingly, while penicillin showed better microbial inhibition than the RDLPMs and Re groups in vitro, the RDLPMs were more effective in vivo. Conclusion: The RDLPMs showed good powder properties for pulmonary delivery. The RDLPMs may inhibit the nuclear factor kappa-B pathway and downregulate the expression of cytokines downstream of tumor necrosis factor-α and interleukin-1ß. As well as, RDLPMs demonstrated some antibacterial properties against A. baumannii bacteria. Re, when delivered in RDLPMs as a dry powder inhaler, is a promising substitute for antibiotics in the treatment of A. baumannii pneumonia.

Rare tumors: a blue ocean of investigation.

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

The complete chloroplast genome sequence of Salix kochiana Trautv. and its phylogenetic analysis.

Salix kochiana Trautvetter 1837 is one of the highest value shrubs present in northern China with important economic and ecological benefits. This study revealed the structural characteristics and phylogenetic relationships of chloroplast genes in S. kochiana Trautv. The results showed that the length of the complete chloroplast genome was 155,657 bp, which was a typical circular double-stranded structure, including an 84,458 bp large single-copy region (LSC), a 16,221 bp small single-copy region (SSC) and a 27,489 bp pair of inverted repeat regions (IRA and IRB). The chloroplast genome contains 48,757 A bases, 28,017 G bases, 49,843 T bases, and 29,040 C bases, with a GC content of 36.66%. Through bioinformatics annotation, a total of 126 genes were found in the chloroplast genome, including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that S. kochiana Trautv. was closely related to S. triandroides.