Investigating the long-term response of plateau vegetation productivity to extreme climate: insights from a case study in Qinghai Province, China.

Over the past three decades, there has been a significant global climate change characterized by an increase in the intensity and frequency of extreme climate events. The vegetation status in Qinghai Province has undergone substantial changes, which are more pronounced than other regions in the Qinghai-Tibet Plateau. However, a clear understanding of the response characteristics of plateau vegetation to extreme climate events is currently lacking. In this study, we investigated the response of net primary productivity (NPP) to different forms of extreme climate events across regions characterized by varying levels of aridity and elevation gradients. Specifically, we observed a significant increase in NPP in relatively arid regions. Our findings indicate that, in relatively arid regions, single episodes of high-intensity precipitation have a pronounced positive effect (higher correlation) on NPP. Furthermore, in high-elevation regions (4000-6000 m), both the intensity and frequency of precipitation events are crucial factors for the increase in regional NPP. However, continuous precipitation can have significant negative impacts on certain areas within relatively wet regions. Regarding temperature, a reduction in the number of frost days within a year has been shown to lead to a significant increase in NPP in arid regions. This reduction allows vegetation growth rate to increase in regions where it was limited by low temperatures. Vegetation conditions in drought-poor regions are expected to continue to improve as extreme precipitation intensifies and extreme low-temperature events decrease.

Loss of FEZ1, a gene deleted in Jacobsen syndrome, causes locomotion defects and early mortality by impairing motor neuron development.

FEZ1-mediated axonal transport plays important roles in central nervous system development but its involvement in the peripheral nervous system is not well-characterized. FEZ1 is deleted in Jacobsen syndrome (JS), an 11q terminal deletion developmental disorder. JS patients display impaired psychomotor skills, including gross and fine motor delay, suggesting that FEZ1 deletion may be responsible for these phenotypes, given its association with the development of motor-related circuits. Supporting this hypothesis, our data show that FEZ1 is selectively expressed in the rat brain and spinal cord. Its levels progressively increase over the developmental course of human motor neurons (MN) derived from embryonic stem cells. Deletion of FEZ1 strongly impaired axon and dendrite development, and significantly delayed the transport of synaptic proteins into developing neurites. Concurring with these observations, Drosophila unc-76 mutants showed severe locomotion impairments, accompanied by a strong reduction of synaptic boutons at neuromuscular junctions. These abnormalities were ameliorated by pharmacological activation of UNC-51/ATG1, a FEZ1-activating kinase, with rapamycin and metformin. Collectively, the results highlight a role for FEZ1 in MN development and implicate its deletion as an underlying cause of motor impairments in JS patients.

Covered stent treatment for arterial complications after pancreatic surgery: risk assessment for recurrence and peri-stent implantation management.

OBJECTIVES: To explore the risk factors for recurrence of arterial complications after pancreatectomy during the period of covered stent implantation and to provide some opinions on peri-stent implantation management. METHODS: Data on patients implanted with covered stents due to arterial complications after pancreatectomy between January 2017 and December 2021 were analyzed retrospectively. Technical success, clinical success, recurrence, and survival were evaluated to elucidate the practicability of covered stents. Wilson score, Random Forest, logistic regression, and Pearson's chi-square test with bootstrap aggregation were performed for determining the perioperative risk factors for recurrence. RESULTS: Among all fifty-five patients, success stent implantation (technical success) was achieved 100%. Patients who were hemodynamically stabilized without further treatment for artery complications in situ (clinical success) accounted for 89.1%. Based on statistical analysis, pre-stent implantation pancreatic fistula was identified as a robust recurrence-related risk factor for preoperative assessment (p = 0.02, OR = 4.5, 95% CI [1.2, 16.9]; pbootstrap = 0.02). Post-stent implantation pancreatic fistula (p = 0.01, OR 4.5, 95% CI [1.4, 14.6]; pbootstrap < 0.05) and SMA branches or GDA stumps (p = 0.02, OR 3.4, 95% CI [1.1, 10.3]) were relevant to recurrence. The survival rate during hospitalization was 87.3%. All survivors were free from recurrence during the subsequent follow-up. Vasospasm and stent occlusion were observed as short-term and long-term complications, respectively. CONCLUSION: A covered stent implantation is a feasible and effective treatment option for post-pancreatectomy arterial complications. Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis. KEY POINTS: • A covered stent is feasible for various artery-related complications after pancreatectomy and has an ideal therapeutic effect. • Pancreatic fistula during the perioperative period of the covered stent is an independent risk factor for recurrent arterial complications and SMA branches or GDA stumps are prone to be recurrent offending arteries. • Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis.

HNRNPC regulates RhoA to induce DNA damage repair and cancer-associated fibroblast activation causing radiation resistance in pancreatic cancer.

Pancreatic cancer (PC) is one of the most lethal types of cancer due to its asymptomatic nature in the early stages and consequent late diagnosis. Its mortality rate remains high despite advances in treatment strategies, which include a combination of surgical resection and adjuvant therapy. Although these approaches may have a positive effect on prognosis, the development of chemo- and radioresistance still poses a significant challenge for successful PC treatment. Heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) and RhoA have been implicated in the regulation of tumour cell proliferation and chemo- and radioresistance. Our study aims to investigate the mechanism for HNRNPC regulation of PC radiation resistance via the RhoA pathway. We found that HNRNPC and RhoA mRNA and protein expression levels were significantly higher in PC tissues compared to adjacent non-tumour tissue. Furthermore, high HNRNPC expression was associated with poor patient prognosis. Using HNRNPC overexpression and siRNA interference, we demonstrated that HNRNPC overexpression promoted radiation resistance in PC cells, while HNRNPC knockdown increased radiosensitivity. However, silencing of RhoA expression was shown to attenuate radiation resistance caused by HNRNPC overexpression. Next, we identified RhoA as a downstream target of HNRNPC and showed that inhibition of the RhoA/ROCK2-YAP/TAZ pathway led to a reduction in DNA damage repair and radiation resistance. Finally, using both in vitro assays and an in vivo subcutaneous tumour xenograft model, we demonstrated that RhoA inhibition can hinder the activity of cancer-related fibroblasts and weaken PC radiation resistance. Our study describes a role for HNRNPC and the RhoA/ROCK2-YAP/TAZ signalling pathways in mediating radiation resistance and provides a potential therapeutic target for improving the treatment of PC.

The single flagellum of Leishmania has a fixed polarisation of its asymmetric beat.

Eukaryotic flagella undertake different beat types as necessary for different functions; for example, the Leishmania parasite flagellum undergoes a symmetric tip-to-base beat for forward swimming and an asymmetric base-to-tip beat to rotate the cell. In multi-ciliated tissues or organisms, the asymmetric beats are coordinated, leading to movement of the cell, organism or surrounding fluid. This coordination involves a polarisation of power stroke direction. Here, we asked whether the asymmetric beat of the single Leishmania flagellum also has a fixed polarisation. We developed high frame rate dual-colour fluorescence microscopy to visualise flagellar-associated structures in live swimming cells. This showed that the asymmetric Leishmania beat is polarised, with power strokes only occurring in one direction relative to the asymmetric flagellar machinery. Polarisation of bending was retained in deletion mutants whose flagella cannot beat but have a static bend. Furthermore, deletion mutants for proteins required for asymmetric extra-axonemal and rootlet-like flagellum-associated structures also retained normal polarisation. Leishmania beat polarisation therefore likely arises from either the nine-fold rotational symmetry of the axoneme structure or is due to differences between the outer doublet decorations.

Leishmania flagellum attachment zone is critical for flagellar pocket shape, development in the sand fly, and pathogenicity in the host.

Leishmania kinetoplastid parasites infect millions of people worldwide and have a distinct cellular architecture depending on location in the host or vector and specific pathogenicity functions. An invagination of the cell body membrane at the base of the flagellum, the flagellar pocket (FP), is an iconic kinetoplastid feature, and is central to processes that are critical for Leishmania pathogenicity. The Leishmania FP has a bulbous region posterior to the FP collar and a distal neck region where the FP membrane surrounds the flagellum more closely. The flagellum is attached to one side of the FP neck by the short flagellum attachment zone (FAZ). We addressed whether targeting the FAZ affects FP shape and its function as a platform for host-parasite interactions. Deletion of the FAZ protein, FAZ5, clearly altered FP architecture and had a modest effect in endocytosis but did not compromise cell proliferation in culture. However, FAZ5 deletion had a dramatic impact in vivo: Mutants were unable to develop late-stage infections in sand flies, and parasite burdens in mice were reduced by >97%. Our work demonstrates the importance of the FAZ for FP function and architecture. Moreover, we show that deletion of a single FAZ protein can have a large impact on parasite development and pathogenicity.

Conditional disruption of AMP kinase in dopaminergic neurons promotes Parkinson's disease-associated phenotypes in vivo.

Emerging studies implicate energy dysregulation as an underlying trigger for Parkinson's disease (PD), suggesting that a better understanding of the molecular pathways governing energy homeostasis could help elucidate therapeutic targets for the disease. A critical cellular energy regulator is AMP kinase (AMPK), which we have previously shown to be protective in PD models. However, precisely how AMPK function impacts on dopaminergic neuronal survival and disease pathogenesis remains elusive. Here, we showed that Drosophila deficient in AMPK function exhibits PD-like features, including dopaminergic neuronal loss and climbing impairment that progress with age. We also created a tissue-specific AMPK-knockout mouse model where the catalytic subunits of AMPK are ablated in nigral dopaminergic neurons. Using this model, we demonstrated that loss of AMPK function promotes dopaminergic neurodegeneration and associated locomotor aberrations. Accompanying this is an apparent reduction in the number of mitochondria in the surviving AMPK-deficient nigral dopaminergic neurons, suggesting that an impairment in mitochondrial biogenesis may underlie the observed PD-associated phenotypes. Importantly, the loss of AMPK function enhances the susceptibility of nigral dopaminergic neurons in these mice to 6-hydroxydopamine-induced toxicity. Notably, we also found that AMPK activation is reduced in post-mortem PD brain samples. Taken together, these findings highlight the importance of neuronal energy homeostasis by AMPK in PD and position AMPK pathway as an attractive target for future therapeutic exploitation.

Hypoxia-induced Tie1 drives stemness and cisplatin resistance in non-small cell lung carcinoma cells.

BACKGROUND: Drug resistance and metastasis involving hypoxic tumor environments and persistent stem cell populations are detrimental to the survival of patients with non-small cell lung carcinoma (NSCLC). Tie1 is upregulated in hypoxia and is believed to counteract the effectiveness of platinum agents by promoting the stemness properties in cells. We have investigated the association of Tie1 with HIF-1α and cisplatin resistance in NSCLC cell lines. METHODS: The expression of Tie1 in a pulmonary microvascular endothelial cell line (HPMEC) and NSCLC cell lines was detected using qRT-PCR and western blotting. The effect of Tie1 on cell stemness and migration was examined by sphere-forming and transwell assays in NSCLC cells with Tie1 silenced. The regulation of Tie1 by HIF-1α was evaluated by a dual-luciferase reporter assay and chromatin immunoprecipitation. RESULTS: We found that hypoxia could induce stemness and cisplatin resistance in vitro. Tie1 was expressed at low levels in NSCLC cells when compared with human pulmonary microvascular endothelial cells, however, its expression was increased by hypoxia. Additionally, Tie1 knockdown could reduce stemness properties and increase sensitivity to cisplatin in vitro and in a xenograft mouse model. The promoter of Tie1 contains two predicted hypoxia-response elements (HREs). We mutated both HRE sites and conducted chromatin immune-precipitation and promoter luciferase reporter assays and were able to conclude that the induction of Tie1 by hypoxia was HIF-1α-dependent. CONCLUSIONS: Our findings indicated that Tie1 is upregulated in a hypoxic environment by HIF-1α and contributes to tumorigenesis and cisplatin resistance through the promotion of stemness in NSCLC cells.

A retrospective study of CT-guided percutaneous irreversible electroporation (IRE) ablation: clinical efficacy and safety.

BACKGROUND: To evaluate the clinical efficacy and safety of ablating renal cell carcinoma (RCC) by irreversible electroporation (IRE). METHODS: Fifteen patients (19 lesions) with RCC who underwent IRE were retrospectively reviewed. Seven patients had solitary kidneys. Two lesions were located in the renal hilus. One patient had chronic renal insufficiency. Percutaneous biopsy for histopathology was performed. The best puncture path plan was evaluated before CT-guided IRE. The estimated glomerular filtration rate (eGFR) was compared vs baseline at 1-2 months after the ablation. Contrast-enhanced computed tomography imaging changes were evaluated immediately after IRE. Contrast-enhanced computed tomography/magnetic resonance was performed 1 month, 3 months, 6 months, 12 months and every year thereafter. The complications after treatment were also reviewed. RESULTS: The success rate of the procedure was 100%. The median tumor size was 2.4 (IQR 1.3-2.9) cm, with an median score of 6 (IQR 5.5-8) per R.E.N.A.L. criteria (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines). Two cases (3 lesions) were punctured through the liver. In other cases, puncture was performed through the perirenal space. There were no severecomplications in interventional therapy. Transient gross hematuria occurred in 2 patients (centrally located). Self-limiting perinephric hematomas occurred in 1 patient. Needle puncture path metastasis was found in 1 patient 2.5 years after IRE. The subcutaneous metastasis was surgically removed, and there was no evidence of recurrence. There was no significant change in eGFR levels in terms of short- term clinical outcomes (t = 0.348, P = 0.733). At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 15) was noted to have experienced needle tract metastasis and accepted salvage radiofrequency ablation (RFA) therapy. CONCLUSIONS: IRE appears to be a safe and effective treatment for RCC that may offer a tissue-sparing method and complete ablation as an alternative therapy for RCC.

Long-term agricultural contamination shaped diversity response of sediment microbiome.

The pollution caused by agricultural production poses a threat to the ecological integrity of river ecosystems, altering the structure and function of river ecosystems. Differences in microbial community structure provide useful information about the impact of agricultural pollution on the biological integrity of ecosystems, but generally convey little information regarding ecosystem functions. In this study, using Illumina MiSeq sequencing technology based on the 16S rRNA gene, river sediment samples associated with four different types of agricultural pollution were comprehensively analyzed. The results show that the total organic carbon (TOC) content was highest at the YZS site (animal husbandry sewage) among the assayed sites, but the species richness and uniformity were lowest at this site, which may have been caused by the high nutrient source of the sewage. Furthermore, in the three YZS samples affected by the long-term discharge of aquaculture tail-water, the unique genus Dechloromonas and the genus Candidatus-Competitor were observed, which are strongly correlated with phosphorus conversion. The formation of network modules may correspond to the coexistence of functional bacteria accustomed to multiple niche combinations under different agricultural pollution conditions in river sediments. According to the PICRUSt functional prediction, the bacterial community in the agricultural polluted river sediment primarily harbored 46 subfunctions, exhibiting richness of functions. Overall, our results provide a more comprehensive understanding of the structure and ecological processes associated with the aggregation of bacterial communities, which is beneficial for the management of river environments.

A novel technique of percutaneous transhepatic treatment of biliary-enteric anastomotic occlusive strictures with compliant balloon-occluded distal cholangiography and large-bore catheter: a retrospective case series.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary balloon dilatation (PTBD) is a challenge in resolving biliary-enteric anastomotic occlusive strictures (BEAOS) and/or coexisting stones. The biliary-enteric anastomosis (BEA) often cannot be seen because of the surgically altered gastrointestinal anatomy. Here, a technique that combined percutaneous compliant-occluded distal cholangiography and the maintenance of a large-bore catheter is described to resolve this issue. Methods: A retrospective review of 10 patients who presented with BEAOS with/without coexisting stones who were treated with percutaneous compliant balloon-occluded distal cholangiography, bile duct stone removal, and the maintenance of a large-bore catheter between February 2017 and January 2021 was performed. Treatment response, laboratory examinations, including hepatic function tests, routine blood tests, and blood electrolytes, complications, and imaging data were evaluated. Paired t-tests were used to investigate the difference of laboratory examinations before and after the procedure. Results: All 10 cases were technically successful. A total of 9 stones in 6 patients were successfully removed by the compliant balloon. All catheters were removed after the patency of the stricture was confirmed by percutaneous transhepatic cholangiography (PTHC) 6 months later. No severe adverse events occurred during the perioperative period. There were 2 patients who experienced episodes of cholangitis during the follow-up period (mean, 17 months; range, 4-24 months), and neither BEAOS nor bile duct stones recurred within 2 years after the procedure. White blood cells (WBC), total bilirubin (TB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were (6.0±1.4)×109/L and (6.0±1.6)×109/L (P=0.91), 31.4±15.7 and 29.6±10.3 µmol/L (P=0.74), 50.8±20.0 and 85.8±67.0 U/L (P=0.16), and 42.6±15.2 and 71.8±44.9 U/L (P=0.09) pre and postintervention, respectively. Conclusions: Percutaneous transhepatic compliant balloon-occluded distal cholangiography and the maintenance of a large-bore catheter probably provide an effective and safe alternative method for resolving BEAOS and/or coexisting stones.

Selection of endovascular treatment strategies and analysis of the efficacy of different locations and types of splenic artery aneurysms.

PURPOSE: To analyze the selection of endovascular treatment strategies and the efficacy of various locations and types of splenic artery aneurysms (SAAs). METHODS: Sixty-three cases of patients diagnosed with SAA from January 2016 to October 2021 were collected, and their clinical data and follow-up results were analyzed. RESULTS: Among the 63 patients, 55 had true SAAs, and 8 had false SAAs. The average diameter of the true SAAs was 2.0 ± 0.8 cm. There were 10 cases of intra-aneurysm embolization, 24 cases of intra-aneurysm and aneurysm-bearing artery embolization, 10 cases of bare stent-assisted coil embolization, and 11 cases of stent grafts. The false SAAs had an average diameter of 2.3 ± 1.1 cm. Aneurysm-bearing artery embolization was applied in 5 cases, and stent grafts were applied in 3 cases. The incidence of complications after embolization of the aneurysm-bearing artery was higher (P < 0.01). Postembolization syndrome occurred in 10 patients; 7 patients developed splenic infarction to varying degrees, 1 patient had mildly elevated blood amylase, and 1 patient developed splenic necrosis with abscess formation, all of which improved after active treatment. The average length of hospital stay was 5.5 ± 3.2 days. The average follow-up time was 17.2 ± 16.1 months, and the aneurysm cavity of all patients was completely thrombotic. CONCLUSION: Endovascular treatments of SAAs are safe and effective. For various locations and types of SAAs, adequate selection of treatment is necessary. Stent grafts are recommended for their safety, economy, practicality, and preservation of the physiological functions of the human body.

IL-1α is required for T cell-driven weight loss after respiratory viral infection.

Respiratory viral infections remain a major cause of hospitalization and death worldwide. Patients with respiratory infections often lose weight. While acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection-induced weight loss, its mechanism is not yet completely understood. We utilized a model of CD 8+ T cell-driven weight loss during respiratory syncytial virus (RSV) infection to dissect the immune regulation of post-infection weight loss. Supporting previous data, bulk RNA sequencing indicated significant enrichment of the interleukin (IL)-1 signaling pathway after RSV infection. Despite increased viral load, infection-associated weight loss was significantly reduced after IL-1α (but not IL-1ß) blockade. IL-1α depletion resulted in a reversal of the gut microbiota changes observed following RSV infection. Direct nasal instillation of IL-1α also caused weight loss. Of note, we detected IL-1α in the brain after either infection or nasal delivery. This was associated with changes in genes controlling appetite after RSV infection and corresponding changes in signaling molecules such as leptin and growth/differentiation factor 15. Together, these findings indicate a lung-brain-gut signaling axis for IL-1α in regulating weight loss after RSV infection.

Systemic prime mucosal boost significantly increases protective efficacy of bivalent RSV influenza viral vectored vaccine.

Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.

Chromosome-level genome assembly of the endangered plant Tetraena mongolica.

Tetraena mongolica is an endangered xerophytic shrub with high ecological value for the restoration of desert vegetation because of its high tolerance to drought and heat stress. Here, we generated a high-quality chromosome-level reference genome of T. mongolica by combining PacBio HiFi data and Hi-C sequencing technologies, which was approximately 1.12 Gb (contig N50 of 25.5 Mb) in size and contained 61,888 protein-coding genes; repetitive sequences comprised 44.8% of the genome. This genome of T. mongolica is the first published genome sequence of a member of the order Zygophyllales. Genome analysis showed that T. mongolica has undergone a recent whole genome duplication event, and a recent burst of long terminal repeat insertions afterward, which may be responsible for its genome size expansion and drought adaptation. We also conducted searches for gene homologues and identified terpene synthase (TPS) gene families and candidate genes involved in triacylglycerol biosynthesis. The T. mongolica genome sequence could aid future studies aimed at functional gene identification, germplasm resource management, molecular breeding efforts, as well as evolutionary studies of Fabids and angiosperm taxa.

Comparison of core needle biopsy and fine-needle aspiration methods in CT-guided percutaneous sampling of pancreatic tumors.

Aims: To compare the diagnostic efficacy and safety of CT-guided percutaneous core needle biopsy (CNB) and fine-needle aspiration (FNA) for pancreatic lesions. Methods and Material: A total of 176 patients with 176 pancreatic lesions who visited our hospital between January 2016 and March 2021 were retrospectively analyzed. They were divided into three groups: FNA group A (<1.5 cm between the lesion and great vessels necessitating FNA), FNA group B, and CNB (the latter two with ≥1.5 cm between the lesion and great vessels necessitating FNA). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and postoperative. The statistical analysis was done using Statistical Package for the Social Sciences version 17.0. Results: One hundred and seventy six patient's specimens all met the requirements. There were no statistically significant differences in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy between the CNB group and FNA group B, (P > 0.05). Thirteen samples submitted for genetic testing (5 in CNB group, 4 in each of the FNA groups A and B) all met the standards of next-generation sequencing gene detection. The main complications of these groups included abdominal pain, fever, and hyperamylasemia. Conclusions: CT-guided percutaneous FNA and CNB have similar diagnostic efficacy for pancreatic biopsy. Furthermore, FNA has a wide range of puncture indications and is very safe. Like CNB, the obtained tissue through FNA can be genetically tested to guide clinical treatment.

Computed Tomography-guided Percutaneous Lung Biopsy With Electromagnetic Navigation Compared With Conventional Approaches: An Open-label, Randomized Controlled Trial.

PURPOSE: The purpose of this study was to assess the efficiency and safety of computed tomography (CT)-guided percutaneous biopsy of lung lesions with electromagnetic (EM) navigation and compare them with those of conventional approaches. MATERIALS AND METHODS: Seventy-nine patients with lung or liver lesions who needed biopsies were enrolled in this trial. All patients were randomly assigned to the E group underwent CT-guided percutaneous biopsies with the EM navigation system or to the C group treated with conventional approaches. RESULTS: In total, 27 patients with lung lesions were assigned to the E group, and 20 patients were assigned to the C group. The diagnostic success rate was 92.6% and 95% in both groups, respectively (P>0.9999). The median number of needle repositions in the E group was less than that in the C group (2.0 vs. 2.5, P=0.03). The positioning success rate with 1 or 2 needle repositions for the E group was significantly higher than the C group (81.5% vs. 50%, P=0.03). The median accuracy of the puncture location in the E group was better than that in the C group (2.0 vs. 6.6 mm, P<0.0001). The total procedure time lengthened in the E group compared with the C group (30.5±1.6 vs. 18.3±1.7 min, P<0.0001), but the number of CT acquisitions was not significantly different (P=0.08). There was no significant difference in complication incidence between the 2 groups (P=0.44). CONCLUSION: The EM navigation system is an effective and safe auxiliary tool for CT-guided percutaneous lung biopsy, but lengthen the procedure time. TRIAL REGISTRATION: ChiCTR2100043361, registered February 9, 2021-retrospectively registered (http://www.medresman.org.cn/uc/project/projectedit.aspx?proj=7591).

Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines.

To be effective, RNA vaccines require both in situ translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. We investigated how formulation affects the acute systemic cytokine response to a self-amplifying RNA (saRNA) vaccine. We compared a cationic polymer (pABOL), a lipid emulsion (nanostructured lipid carrier, NLC), and three lipid nanoparticles (LNP). After immunization, we measured serum cytokines and compared the response to induced antibodies against influenza virus. Formulations that induced a greater cytokine response induced a greater antibody response, with a significant correlation between IP-10, MCP-1, KC, and antigen-specific antibody titers. We then investigated how innate immune sensing and signaling impacted the adaptive immune response to vaccination with LNP-formulated saRNA. Mice that lacked MAVS and are unable to signal through RIG-I-like receptors had an altered cytokine response to saRNA vaccination and had significantly greater antibody responses than wild-type mice. This indicates that the inflammation induced by formulated saRNA vaccines is not solely deleterious in the induction of antibody responses and that targeting specific aspects of RNA vaccine sensing might improve the quality of the response.

Propylene glycol inactivates respiratory viruses and prevents airborne transmission.

Viruses are vulnerable as they transmit between hosts, and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates a broad range of viruses including influenza A, SARS-CoV-2 and rotavirus and reduces disease burden in mice when administered intranasally at concentrations commonly found in nasal sprays. Most critically, vaporised PG efficiently abolishes influenza A virus and SARS-CoV-2 infectivity within airborne droplets, potently preventing infection at levels well below those tolerated by mammals. We present PG vapour as a first-in-class non-toxic airborne virucide that can prevent transmission of existing and emergent viral pathogens, with clear and immediate implications for public health.

Reducing cell intrinsic immunity to mRNA vaccine alters adaptive immune responses in mice.

The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment, but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines. In the current study, we compared mRNA vaccines in mice against influenza virus using three different mRNA formats: uridine-containing mRNA (D1-uRNA), m1Ψ-modified mRNA (D1-modRNA), and D1-modRNA with a cap1 structure (cC1-modRNA). D1-uRNA vaccine induced a significantly different gene expression profile to the modified mRNA vaccines, with an up-regulation of Stat1 and RnaseL, and increased systemic inflammation. This result correlated with significantly reduced antigen-specific antibody responses and reduced protection against influenza virus infection compared with D1-modRNA and cC1-modRNA. Incorporation of m1Ψ alone without cap1 improved antibodies, but both modifications were required for the optimum response. Therefore, the incorporation of m1Ψ and cap1 alters protective immunity from mRNA vaccines by altering the innate immune response to the vaccine material.