Ultradynamic Isoreticularly Expanded Porous Organic Crystals.

Porous organic materials showcasing large framework dynamics present new paths for adsorption and separation with enhanced capacity and selectivity beyond the size-sieving limits, which is attributed to their guest-responsive sorption behaviors. Porous hydrogen-bonded crosslinked organic frameworks (HCOFs) are attractive for their remarkable ability to undergo guest-triggered expansion and contraction facilitated by their flexible covalent crosslinkages. However, the voids of HCOFs remain limited, which restrains the extent of the framework dynamics. In this work, we synthesized a series of HCOFs characterized by unprecedented size expansion capabilities induced by solvents. These HCOFs were constructed by isoreticularly co-crystallizing two complementary sets of hydrogen bonding building blocks to generate porous molecular crystals, which were crosslinked through thiol-ene/yne single-crystal-to-single-crystal transformations. The generated HCOFs exhibit enhanced chemical durability, high crystallinity, and extraordinary framework dynamics. For instance, HCOF-104 crystals featuring a pore diameter of 13.6 Å expanded in DMF to 300 ± 10% of their original lengths within just 1 min. This expansion allows the HCOFs to adsorb guest molecules that are significantly larger than the pore sizes of their crystalline states. Through methanol-induced contraction, these large guests were encapsulated in the fast-contracted HCOFs. These advancements in porous framework dynamics pave the way for new methods of encapsulating guests for targeted delivery.

An analysis of the potential association between obstructive sleep apnea and osteoporosis from the perspective of transcriptomics and NHANES.

BACKGROUND: Obstructive sleep apnea (OSA) and osteoporosis (OP) are prevalent diseases in the elderly. This study aims to reveal the clinical association between OSA and OP and explore potential crosstalk gene targets. METHODS: Participants diagnosed with OSA in the National Health and Nutrition Examination Survey (NHANES) database (2015-2020) were included, and OP was diagnosed based on bone mineral density (BMD). We explored the association between OSA and OP, and utilized multivariate logistic regression analysis and machine learning algorithms to explore the risk factors for OP in OSA patients. Overlapping genes of comorbidity were explored using differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Random Forest (RF) methods. RESULTS: In the OSA population, the weighted prevalence of OP was 7.0%. The OP group had more females, lower body mass index (BMI), and more low/middle-income individuals compared to the non-OP group. Female gender and lower BMI were identified as independent risk factors for OP in OSA patients. Gene expression profiling revealed 8 overlapping differentially expressed genes in OP and OSA patients. KCNJ1, NPR3 and WT1-AS were identified as shared diagnostic biomarkers or OSA and OP, all of which are associated with immune cell infiltration. CONCLUSION: This study pinpointed female gender and lower BMI as OP risk factors in OSA patients, and uncovered three pivotal genes linked to OSA and OP comorbidity, offering fresh perspectives and research targets.

Elastic Relaxor Ferroelectric by Thiol-ene Click Reaction.

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

Structural basis for the recognition of methylated histone H3 by the Arabidopsis LHP1 chromodomain.

Arabidopsis LHP1 (LIKE HETEROCHROMATIN PROTEIN 1), a unique homolog of HP1 in Drosophila, plays important roles in plant development, growth, and architecture. In contrast to specific binding of the HP1 chromodomain to methylated H3K9 histone tails, the chromodomain of LHP1 has been shown to bind to both methylated H3K9 and H3K27 histone tails, and LHP1 carries out its function mainly via its interaction with these two epigenetic marks. However, the molecular mechanism for the recognition of methylated histone H3K9/27 by the LHP1 chromodomain is still unknown. In this study, we characterized the binding ability of LHP1 to histone H3K9 and H3K27 peptides and found that the chromodomain of LHP1 binds to histone H3K9me2/3 and H3K27me2/3 peptides with comparable affinities, although it exhibited no binding or weak binding to unmodified or monomethylated H3K9/K27 peptides. Our crystal structures of the LHP1 chromodomain in peptide-free and peptide-bound forms coupled with mutagenesis studies reveal that the chromodomain of LHP1 bears a slightly different chromodomain architecture and recognizes methylated H3K9 and H3K27 peptides via a hydrophobic clasp, similar to the chromodomains of human Polycomb proteins, which could not be explained only based on primary structure analysis. Our binding and structural studies of the LHP1 chromodomain illuminate a conserved ligand interaction mode between chromodomains of both animals and plants, and shed light on further functional study of the LHP1 protein.

A Systematic Review of Polycyclic Aromatic Hydrocarbon Derivatives: Occurrences, Levels, Biotransformation, Exposure Biomarkers, and Toxicity.

Polycyclic aromatic hydrocarbon (PAH) derivatives constitute a significant class of emerging contaminants that have been ubiquitously detected in diverse environmental matrixes, with some even exhibiting higher toxicities than their corresponding parent PAHs. To date, compared with parent PAHs, fewer systematic summaries and reanalyses are available for PAH derivatives with great environmental concerns. This review summarizes the current knowledge on the chemical species, levels, biotransformation patterns, chemical analytical methods, internal exposure routes with representative biomarkers, and toxicity of PAH derivatives, primarily focusing on nitrated PAHs (NPAHs), oxygenated PAHs (OPAHs), halogenated PAHs (XPAHs), and alkylated PAHs (APAHs). A collection of 188 compounds from four categories, 44 NPAHs, 36 OPAHs, 56 APAHs, and 52 XPAHs, has been compiled from 114 studies that documented the environmental presence of PAH derivatives. These compounds exhibited weighted average air concentrations that varied from a lower limit of 0.019 pg/m3 to a higher threshold of 4060 pg/m3. Different analytical methods utilizing comprehensive two-dimensional gas chromatography coupled with high-resolution time-of-flight mass spectrometry (GC × GC-TOF-MS), gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS), comprehensive two-dimensional gas chromatography coupled to quadrupole mass spectrometry (GC × GC-QQQ-MS), and Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), that adopted untargeted strategies for the identification of PAH derivatives are also reviewed here. Additionally, an in-depth analysis of biotransformation patterns for each category is provided, including the likelihood of specific biotransformation reaction types. For the toxicity, we primarily summarized key metabolic activation pathways, which could result in the formation of reactive metabolites capable of covalently bonding with DNA and tissue proteins, and potential health outcomes such as carcinogenicity and genotoxicity, oxidative stress, inflammation and immunotoxicity, and developmental toxicity that might be mediated by the aryl hydrocarbon receptor (AhR). Finally, we pinpoint research challenges and emphasize the need for further studies on identifying PAH derivatives, tracking external exposure levels, evaluating internal exposure levels and associated toxicity, clarifying exposure routes, and considering mixture exposure effects. This review aims to provide a broad understanding of PAH derivatives' identification, environmental occurrence, human exposure, biotransformation, and toxicity, offering a valuable reference for guiding future research in this underexplored area.

Ortho-Alkoxy-benzamide Directed Formation of a Single Crystalline Hydrogen-bonded Crosslinked Organic Framework and Its Boron Trifluoride Uptake and Catalysis.

Boron trifluoride (BF3 ) is a highly corrosive gas widely used in industry. Confining BF3 in porous materials ensures safe and convenient handling and prevents its degradation. Hence, it is highly desired to develop porous materials with high adsorption capacity, high stability, and resistance to BF3 corrosion. Herein, we designed and synthesized a Lewis basic single-crystalline hydrogen-bond crosslinked organic framework (HC OF-50) for BF3 storage and its application in catalysis. Specifically, we introduced self-complementary ortho-alkoxy-benzamide hydrogen-bonding moieties to direct the formation of highly organized hydrogen-bonded networks, which were subsequently photo-crosslinked to generate HC OFs. The HC OF-50 features Lewis basic thioether linkages and electron-rich pore surfaces for BF3 uptake. As a result, HC OF-50 shows a record-high 14.2 mmol/g BF3 uptake capacity. The BF3 uptake in HC OF-50 is reversible, leading to the slow release of BF3 . We leveraged this property to reduce the undesirable chain transfer and termination in the cationic polymerization of vinyl ethers. Polymers with higher molecular weights and lower polydispersity were generated compared to those synthesized using BF3 ⋅ Et2 O. The elucidation of the structure-property relationship, as provided by the single-crystal X-ray structures, combined with the high BF3 uptake capacity and controlled sorption, highlights the molecular understanding of framework-guest interactions in addressing contemporary challenges.

White matter edematous change with moderate vascular lesions in pretreated acute stage of leukoencephalopathy with cerebral amyloid angiopathy.

A 79-year-old man presented with subacute onset of dementia. Brain magnetic resonance imaging revealed leukoencephalopathy in the posterior lobes with presence of microbleeds. Although clinical manifestation suggested a diagnosis of leukoencephalopathy associated with cerebral amyloid angiopathy (CAA), the patient died of sudden rupture of an aneurysm of the thoracic aorta two months after the onset of dementia. Autopsy revealed pathological features of advanced-stage Alzheimer's disease. Immunohistochemistry for amyloid-ß revealed CAA mainly affecting arteries but not capillaries. Klüver-Barrera staining revealed white matter edema predominantly in the occipital lobes without ischemic changes. Perivascular cuffing was found to be sparse, but there was no evidence of angiitis. Pathological findings suggest that leukoencephalopathy was caused by the disruption of the blood-brain barrier rather than ischemia. Because the present patient died before immunotherapy, his neuropathological findings could reflect the pathomechanism of the acute stage of leukoencephalopathy with CAA.

Targeting Inflammation and Regeneration: Scaffolds, Extracellular Vesicles, and Nanotechnologies as Cell-Free Dual-Target Therapeutic Strategies.

Osteoarthritis (OA) affects over 250 million people worldwide and despite various existing treatment strategies still has no cure. It is a multifactorial disease characterized by cartilage loss and low-grade synovial inflammation. Focusing on these two targets together could be the key to developing currently missing disease-modifying OA drugs (DMOADs). This review aims to discuss the latest cell-free techniques applied in cartilage tissue regeneration, since they can provide a more controllable approach to inflammation management than the cell-based ones. Scaffolds, extracellular vesicles, and nanocarriers can be used to suppress inflammation, but they can also act as immunomodulatory agents. This is consistent with the latest tissue engineering paradigm, postulating a moderate, controllable inflammatory reaction to be beneficial for tissue remodeling and successful regeneration.

High-Performance Flexible Self-Powered Photodetectors Utilizing Spontaneous Electron and Hole Separation in Quasi-2D Halide Perovskites.

Although there are recent advances in many areas of quasi-2D halide perovskites, photodetectors based on these materials still cannot achieve satisfactory performance for practical applications where high responsivity, fast response, self-powered nature, and excellent mechanical flexibility are urgently desired. Herein, utilizing one-step spin-coating method, self-assemble quasi-2D perovskite films with graded phase distribution in the order of increasing number of metal halide octahedral layers are successfully prepared. Gradient type-II band alignments along the out-of-plane direction of perovskites with spontaneous separation of photo-generated electrons and holes are obtained and then employed to construct self-powered vertical-structure photodetectors for the first time. Without any driving voltage, the device exhibits impressive performance with the responsivity up to 444 mA W-1 and ultrashort response time down to 52 µs. With a bias voltage of 1.5 V, the device responsivity becomes 3463 mA W-1 with the response speed as fast as 24 µs. Importantly, the device's mechanical flexibility is greatly enhanced since the photocurrent prefers flowing through the metal halide octahedral layers between the top and bottom contact electrodes in the vertical device structure, being more tolerant to film damage. These results evidently indicate the potential of graded quasi-2D perovskite phases for next-generation optoelectronic devices.

Innovative nanochemotherapy for overcoming cancer multidrug resistance.

Tumor multidrug resistance (MDR) is a phenomenon in which drug-resistant tumor cells are resistant to multiple other unexposed antitumor drugs with different structures and targets. MDR of cancer is a primary cause of clinical chemotherapy failure. With the progress of nanotechnology in the medical field, more and more research works have developed many nanotechnology-based strategies to challenge drug resistance. This review details the recent studies at the National Center for Nanoscience and Technology utilizing various nanochemotherapy strategies for overcoming chemotherapy resistance of tumor. We discuss the benefits and limitations of the diverse strategies, as well as possible ways to overcome these limitations. Importantly, in order to combat cancer chemotherapy resistance with nanomedicine, the mechanisms of drug endocytosis and subsequent fate need to be explored and focused on. In the meanwhile, due to the complexity and diversity of chemotherapy resistance mechanisms, the development of more intelligent and controllable nanodrugs may have greater scope for clinical application.

USP28 regulates deubiquitination of histone H2A and cell proliferation.

Post-translational modifications of the histone H2A represent an important mechanism by which cells modulate the structure and function of chromatin. Ubiquitination at K119 of histone H2A is associated transcriptional repression, which is shown to be regulated by deubiquitinases (DUBs). Here, we performed a screen to identify novel DUBs for histone H2A. Although RNAi-mediated knockdown of USP28, USP32 and USP36 showed that their depletion resulted in the increase of ub-K119-H2A, only USP28-depleted cells showed increased cell proliferation. Notably, USP28 knockdown cells had decreased expression of p53, p21 and p16INK4a, suggesting that the effect of USP28 on cell proliferation was mediated by regulating the expression of p53, p21 and p16INK4a. In summary, we have shown that USP28 is a deubiquitinase for histone H2A and is involved in regulation of cell proliferation. Thus, USP28 represents a potentially novel therapeutic target for cancer.

The deubiquitinase OTUD5 regulates Ku80 stability and non-homologous end joining.

The ability of cells to repair DNA double-strand breaks (DSBs) is important for maintaining genome stability and eliminating oncogenic DNA lesions. Two distinct and complementary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are employed by mammalian cells to repair DNA DSBs. Each pathway is tightly controlled in response to increased DSBs. The Ku heterodimer has been shown to play a regulatory role in NHEJ repair. Ku80 ubiquitination contributes to the selection of a DSB repair pathway by causing the removal of Ku heterodimers from DSB sites. However, whether Ku80 deubiquitination also plays a role in regulating DSB repair is unknown. To address this question, we performed a comprehensive study of the deubiquitinase specific for Ku80, and our study showed that the deubiquitinase OTUD5 serves as an important regulator of NHEJ repair by increasing the stability of Ku80. Further studies revealed that OTUD5 depletion impaired NHEJ repair, and hence reduced overall DSB repair. Furthermore, OTUD5-depleted cells displayed excess end resection; as a result, HR repair was facilitated by OTUD5 depletion during the S/G2 phase. In summary, our study demonstrates that OTUD5 is a specific deubiquitinase for Ku80 and establishes OTUD5 as an important and positive regulator of NHEJ repair.

Leaching Behaviour and Enhanced Phytoextraction of Additives for Cadmium-Contaminated Soil by Pennisetum sp.

The leaching behavior of five additives, including citric acid (CA), wood vinegar (WV), 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP), polyaspartic acid (PASP) and FeCl3, was investigated to evaluate the possibility of enhanced phytoextraction of Pennisetum sp. from cadmium-contaminated soil. FeCl3 and CA have the highest leaching potential due to the ability that could convert large amounts of mobile fractions of Cd. The pot experiment showed that HEDP, WV, and PASP treatments could not only significantly increase the biomass of Pennisetum sp., but also maintain high uptake capacity of Cd by activating the stable fractions. HEDP has the highest Cd extraction efficiency and metal extraction ratio (MER) value. The phytoremediation efficiency could be improved mainly by increasing the biomass of the tolerant shoots, and Pennisetum sp. seems to have the maximum potential of phytoextraction to Cd with HEDP which could achieve a higher phytoextraction effect than Cd-hyperaccumulator.

Single-frame-based column fixed-pattern noise correction in an uncooled infrared imaging system based on weighted least squares.

Uncooled infrared images typically suffer from column fixed-pattern noise (FPN), which is introduced by the non-uniformity of the column-parallel readout circuit. It is a challenging task to remove column FPN without introducing stripe artifacts near strong vertical edges. In this paper, we introduce a novel single-frame-based algorithm to accurately correct column FPN. The algorithm contains two 1D filters. First, a 1D weighted least-squares filter is applied to perform edge-preserving filtering in the horizontal direction to obtain a coarse estimation of the clear scene. Then, a local weighted ridge regression is performed between the horizontal smoothed image and the raw infrared image in vertical direction to refine this estimation. Through an analysis on the cause of stripe artifacts, the proposed non-uniformity correction (NUC) algorithm is proved to be effective in eliminating this problem. The performance of our proposed algorithm is thoroughly investigated and compared to four state-of-the-art single-frame-based destriping methods using both simulated and real experiments.

Enhanced Phytoextraction for Co-contaminated Soil with Cd and Pb by Ryegrass (Lolium perenne L.).

A pot experiment was conducted to investigate the effect of three additives - citric acid (CA), polyaspartic acid (PASP), and FeCl3 - on the phytoextraction efficiency of cadmium (Cd) and lead (Pb) by ryegrass (Lolium perenneL.) from artificially contaminated soils with different heavy metal concentrations. The results showed that as the concentration of pollutants increased, the TI (tolerance index) and BCF (bio-concentration factor) of ryegrass gradually increased only when FeCl3 was applied. FeCl3 also exhibited the most significant biomass enhancement and heavy metal accumulation of ryegrass, as well as the highest phytoextraction efficiency in heavily-polluted soils. The overall orders of the optimal phytoextraction efficiency for the three additives in terms of their MER (metal extraction ratio) were: FeCl3 > PASP > CA. Therefore, FeCl3 can be used to improve the Cd and Pb phytoextraction efficiency of ryegrass in heavily-polluted soils.

A comparative study: visual rating scores and the voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging among subjects with Alzheimer's disease, mild cognitive impairment, and normal cognition.

AIM: Hippocampal atrophy shown on magnetic resonance imaging can differentiate Alzheimer's disease (AD) patients from subjects with normal cognition (NC). Simplified automated methods that use volumetric analysis, such as as the voxel-based specific regional analysis system for AD, have become widely used in Japan. However, the diagnostic value of the voxel-based specific regional analysis system compared with visual rating scores for clinical diagnosis is unclear. METHODS: Study participants consisted of 37 AD patients, 29 mild cognitive impairment (MCI) patients, and 21 NC subjects. All participants underwent neuropsychological testing and magnetic resonance imaging. The imaging was scored visually for regional brain atrophy by two raters based on a newly developed visual rating score. The voxel-based specific regional analysis system for AD scores were calculated with the analysis system's advanced software. We analyzed whether these scores aid in discriminating among AD, MCI, and NC. RESULTS: The AD group had significantly different visual rating scores, regional analysis scores, and all neuropsychological test scores than the NC group. The AD group had significantly different visual rating scores than the MCI group, and a significant difference was observed between the MCI and NC groups on regional analysis scores. Both the visual rating and regional analysis scores showed equivalent correlations with the neuropsychological test scores. CONCLUSIONS: Both the visual rating and regional analysis scores are clinically useful tools for differentiating among AD, MCI, and NC.

Quality of randomized controlled trials of new generation antidepressants and antipsychotics identified in the China National Knowledge Infrastructure (CNKI): a literature and telephone interview study.

BACKGROUND: We are witnessing an exponential increase in the number of randomized controlled trials (RCTs) reported from mainland China. The increase is particularly notable in the field of new generation antidepressants and antipsychotics. Several previous studies have raised doubts regarding their quality. However, the quality of most recent RCTs published in China may have improved. METHODS: We searched RCTs that examined new generation antidepressants and antipsychotics published between 2013 and 2016 in the China National Knowledge Infrastructure (CNKI), the largest database of scientific publications in China. We interviewed the authors of a random subset of the identified references. We assessed the methodological rigor of each study based on the published reports and telephone interviews with the authors using six methodological domains adapted from the Cochrane's risk of bias tool. RESULTS: The final sample consisted of 138 studies, for which we interviewed 58 authors; the authors of 51 studies declined the interview, and the authors of 29 studies could not be contacted. The 51 studies with refused interviews were significantly less likely to be reported from university-affiliated hospitals and were less likely to be published in Chinese core journals. Based on the published reports, most of the 58 studies were assessed to be at unclear risk of bias in most methodological domains. After the interview, only 10 studies were assessed to be at low risk of bias for sequence generation and allocation concealment. Assuming that the studies for which the authors declined interviews had an unclear risk, the proportion of RCTs at low risk of bias in both sequence generation and allocation concealment was 9.2% (10/109, 95% confidence interval [CI]: 5.0 to 16.2). The interviews indicated that the studies were at high risk of bias for most of the other domains. CONCLUSION: In general, RCTs that evaluate new generation antidepressants or antipsychotics and are indexed in the CNKI continue to be of low quality. When conducting systematic reviews and meta-analyses in this field, it would be wise to include a specialist from China as a coresearcher to help assess the risk of bias in the identified studies.

Preparation and photocatalytic properties of porous C and N co-doped TiO2 deposited on brick by a fast, one-step microwave irradiation method.

A one-step microwave irradiation method was used to deposit carbon and nitrogen co-doped TiO2 ((C, N)-TiO2) on commercial brick ((C, N)-TiO2/brick). The as-prepared samples were characterized by X-ray diffraction, ultraviolet-visible (UV-vis) diffuse reflectance spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy (SEM). A selective technique was also used to investigate the concentration of hydroxyl radicals during UV-vis irradiation of the Methyl Orange solution with the as-prepared samples. The C and N dopants enhanced visible light absorption and provided a longer lifetime for the photo-generated electron-hole pairs. The SEM images showed that the as-prepared sample is porous. The dark adsorption and photodegradation test for (C, N)-TiO2/brick showed good photodegradation and good recyclability. The best photodegradation rate was 94% after 2hr. The maximum degradation rate was maintained even after the 6th cycle. The good photocatalytic properties are attributed to the enhanced visible light absorption, enhanced pollutant adsorption arising from the porous structure of the (C, N)-TiO2 thin film, and longer lifetime of the photo-generated electron-hole pairs. (C, N)-TiO2/brick should have potential commercial applications in photodegradation processes because of its low cost, good photodegradation, and excellent recyclability.

Lipid levels and low back pain risk: A two-sample mendelian randomization study.

BACKGROUND: Previous observational studies have shown controversial results about the relationship between lipid levels and low back pain (LBP). Herein, we aimed to explore the potential causal relationship between lipid levels and LBP by using the mendelian randomization (MR) analysis. METHODS: In this two-sample MR study, data were extracted from publicly available MRC Integrative Epidemiology Unit database. Three single-nucleotide polymorphisms (SNPs) of lipid levels [high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and two SNPs of LBP risk (LBP and back pain) were retrieved and used as genetic instrumental variables. Inverse-variance weighted (IVW), weighted median, MR-Egger, robust adjusted profile score (MR-RAPS), and MR-PRESSO were used to examine the potential causal association between lipid levels and LBP. RESULTS: IVW (fixed effect) estimation indicated that increased HDL-C level was negatively related to the odds of LBP for European populations. [odds ratio (OR) = 0.923, 95% confidence interval (CI): 0.857-0.993, P = 0.0323]. Similar results were also found in IVW (random effect) (OR = 0.923, 95% CI: 0.866-0.983, P = 0.0134), MR-Egger (OR = 0.858, 95%CI: 0.757-0.973, P = 0.0177), MR-RAPS (OR = 0.932, 95%CI: 0.871-0.997, P = 0.0419), and MR-PRESSO (OR = 0.933, 95%CI: 0.880-0.989, P = 0.0198) analyses. Whereas no causal link was observed between LDL-C/TG and LBP risk (P>0.05). CONCLUSION: This two-sample MR study demonstrated a causal relationship between lipid levels and LBP risk. Further investigations are necessary to elucidate the causal association and specific underlying mechanisms by which lipid levels contribute to the development of LBP.

Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid.

Lipid nanoparticles (LNPs) are currently the most promising clinical nucleic acids drug delivery vehicles. LNPs prevent the degradation of cargo nucleic acids during blood circulation. Upon entry into the cell, specific components of the lipid nanoparticles can promote the endosomal escape of nucleic acids. These are the basic properties of lipid nanoparticles as nucleic acid carriers. As LNPs exhibit hepatic aggregation characteristics, enhancing targeting out of the liver is a crucial way to improve LNPs administrated in vivo. Meanwhile, endosomal escape of nucleic acids loaded in LNPs is often considered inadequate, and therefore, much effort is devoted to enhancing the intracellular release efficiency of nucleic acids. Here, different strategies to efficiently deliver nucleic acid delivery from LNPs are concluded and their mechanisms are investigated. In addition, based on the information on LNPs that are in clinical trials or have completed clinical trials, the issues that are necessary to be approached in the clinical translation of LNPs are discussed, which it is hoped will shed light on the development of LNP nucleic acid drugs.