Resurrection of endogenous retroviruses during aging reinforces senescence.

Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened and contribute to the aging process is largely unknown. In human senescent cells, we found that HERVK (HML-2), the most recently integrated human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young cells, which can be blocked by neutralizing antibodies. The activation of ERVs was also observed in organs of aged primates and mice as well as in human tissues and serum from the elderly. Their repression alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging. These findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging.

Substrate-Switched Dual-Signal Self-Powered Sensing System Based on Dual-Nanozyme Activity of Bimetal-Doped CeO2 Nanospheres for Electrochemical Assay of Aflatoxin B1.

The long-term operation feature of enzymatic biofuel cell-based self-powered biosensor (EBFC-SPB) endows them with the potential to execute dual-signal biosensing without having to integrate an extra signal acquisition device. Herein, cobalt and manganese codoped CeO2 nanospheres (CoMn-CeO2 NSs) with glucose-oxidase-like and peroxidase-like activities have been developed as substrate-switched dual-channel signal transduction components in EBFC-SPB for a dual-signal assay of aflatoxin B1 (AFB1). The CoMn-CeO2 NSs modified with aptamer are anchored to a complementary DNA-attached bioanode of EBFC-SPB by base complementary pairing, which catalyze the glucose oxidation together with the glucose oxidase (GOx) on the bioanode. Once the AFB1 appears, CoMn-CeO2 NSs will be released from the bioanode due to the binding specificity of the aptamer, resulting in a decreased catalytic efficiency and the first declining stage of EBFC-SPB. Accompanied by the introduction of H2O2, the residual CoMn-CeO2 NSs on the bioanode switch to peroxidase-like activity and mediate the production of benzo-4-chlorohexadienone (4-CD) precipitate, which increases the steric hindrance and yields another declining stage of EBFC-SPB. By assessing the variation amplitudes during these two declining stages, the dual-signal assay of AFB1 has been realized with satisfying results. This work not only breaks ground in dual-signal bioassays but also deepens the application of nanozymes in EBFC-SPB.

Strain Effects in Ru-Au Bimetallic Aerogels Boost Electrocatalytic Hydrogen Evolution.

To improve the sluggish kinetics of the hydrogen evolution reaction (HER), a key component in water-splitting applications, there is an urgent desire to develop efficient, cost-effective, and stable electrocatalysts. Strain engineering is proving an efficient strategy for increasing the catalytic activity of electrocatalysts. This work presents the development of Ru-Au bimetallic aerogels by a simple one-step in situ reduction-gelation approach, which exhibits strain effects and electron transfer to create a remarkable HER activity and stability in an alkaline environment. The surface strain induced by the bimetallic segregated structure shifts the d-band center downward, enhancing catalysis by balancing the processes of water dissociation, OH* adsorption, and H* adsorption. Specifically, the optimized catalyst shows low overpotentials of only 24.1 mV at a current density of 10 mA cm-2 in alkaline electrolytes, surpassing commercial Pt/C. This study can contribute to the understanding of strain engineering in bimetallic electrocatalysts for HER at the atomic scale.

The cerebral lymphatic drainage system and its implications in epilepsy.

The central nervous system has long been thought to lack a clearance system similar to the peripheral lymphatic system. Therefore, the clearance of metabolic waste in the central nervous system has been a subject of great interest in neuroscience. Recently, the cerebral lymphatic drainage system, including the parenchymal clearance system and the meningeal lymphatic network, has attracted considerable attention. It has been extensively studied in various neurological disorders. Solute accumulation and neuroinflammation after epilepsy impair the blood-brain barrier, affecting the exchange and clearance between cerebrospinal fluid and interstitial fluid. Restoring their normal function may improve the prognosis of epilepsy. However, few studies have focused on providing a comprehensive overview of the brain clearance system and its significance in epilepsy. Therefore, this review addressed the structural composition, functions, and methods used to assess the cerebral lymphatic system, as well as the neglected association with epilepsy, and provided a theoretical basis for therapeutic approaches in epilepsy.

CmBr confers fruit bitterness under CPPU treatment in melon.

Many biotic or abiotic factors such as CPPU (N-(2-chloro-pyridin-4-yl)-N'-phenylurea), a growth regulator of numerous crops, can induce bitterness in cucurbits. In melon, cucurbitacin B is the major compound leading to bitterness. However, the molecular mechanism underlying CuB biosynthesis in response to different conditions remains unclear. Here, we identified a set of genes involved in CPPU-induced CuB biosynthesis in melon fruit and proposed CmBr gene as the major regulator. Using CRISPR/Cas9 gene editing, we confirmed CmBr's role in regulating CuB biosynthesis under CPPU treatment. We further discovered a CPPU-induced MYB-related transcription factor, CmRSM1, which specifically binds to the Myb motif within the CmBr promoter and activates its expression. Moreover, we developed an introgression line by introducing the mutated Cmbr gene into an elite variety and eliminated CPPU-induced bitterness, demonstrating its potential application in breeding. This study offers a valuable tool for breeding high-quality non-bitter melon varieties and provides new insights into the regulation of secondary metabolites under environmental stresses.

In silico analysis of intestinal microbial instability and symptomatic markers in mice during the acute phase of severe burns.

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

Element Distributions in Bimetallic Aerogels.

ConspectusMetal aerogels assembled from nanoparticles have captured grand attention because they combine the virtues of metals and aerogels and are regarded as ideal materials to address current environmental and energy issues. Among these aerogels, those composed of two metals not only display combinations (superpositions) of the properties of their individual metal components but also feature novel properties distinctly different from those of their monometallic relatives. Therefore, quite some effort has been invested in refining the synthetic methods, compositions, and structures of such bimetallic aerogels as to boost their performance for the envisaged application(s). One such use would be in the field of electrocatalysis, whereby it is also of utmost interest to unravel the element distributions of the (multi)metallic catalysts to achieve a ratio of their bottom-to-up design. Regarding the element distributions in bimetallic aerogels, advanced characterization techniques have identified alloys, core-shells, and structures in which the two metal particles are segregated (i.e., adjacent but without alloy or core-shell structure formation). While an almost infinite number of metal combinations to form bimetallic aerogels can be envisaged, the knowledge of their formation mechanisms and the corresponding element distributions is still in its infancy. The evolution of the observed musters is all but well understood, not to mention the positional changes of the elements observed in operando or in beginning- vs end-of-life comparisons (e.g., in fuel cell applications).With this motivation, in this Account we summarize the endeavors made in element distribution monitoring in bimetallic aerogels in terms of synthetic methods, expected structures, and their evolution during electrocatalysis. After an introductory chapter, we first describe briefly the two most important characterization techniques used for this, namely, scanning transmission electron microscopy (STEM) combined with element mapping (e.g., energy-dispersive X-ray spectroscopy (EDXS)) and X-ray absorption spectroscopy (XAS). We then explain the universal methods used to prepare bimetallic aerogels with different compositions. Those are divided into one-step methods in which gels formed from mixtures of the respective metal salts are coreduced and two-step approaches in which monometallic nanoparticles are mixed and gelated. Subsequently, we summarize the current state-of-knowledge on the element distributions unraveled using diverse characterization methods. This is extended to investigations of the element distributions being altered during electrochemical cycling or other loads. So far, a theoretical understanding of these processes is sparse, not to mention predictions of element distributions. The Account concludes with a series of remarks on current challenges in the field and an outlook on the gains that the field would earn from a solid understanding of the underlying processes and a predictive theoretical backing.

The role of hormones in ILC2-driven allergic airway inflammation.

Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL-5 and IL-13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial-derived alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2-driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.

100 µs Luminescence Lifetime Boosts the Excited State Reactivity of a Ruthenium(II)-Anthracene Complex in Photon Upconversion and Photocatalytic Polymerizations with Red Light.

The triplet excited state lifetime of a photosensitizer is an essential parameter for diffusion-controlled energy- and electron-transfer, which occurs usually in a competitive manner to the intrinsic decay of a triplet excited state. Here we show the decisive role of luminescence lifetime in the triplet excited state reactivity toward energy- and electron transfer. Anchoring two phenyl anthracene chromophores to a ruthenium(II) polypyridyl complex (RuII ref) leads to a RuII triad with a luminescence lifetime above 100 µs, which is more than 40 times longer than that of the prototypical complex. The obtained RuII triad sensitizes energy transfer to anthracene-based annihilators more efficiently than the RuII ref and enables red-to-blue photon upconversion with a pseudo anti-Stokes shift of 0.94 eV and a moderate upconversion efficiency near 1% in aerated solution. Particularly, the RuII triad allows rapid photoredox catalytic polymerizations of acrylate and acrylamide monomers under aerobic condition with red light, which are kinetically hindered for the RuII ref. Our work shows that excited state lifetime of a photosensitizer governs the dynamics of the excited state reactions, which seems an overlooked but important aspect for photochemistry.

Ferromagnetically Coupled Chromium(III) Dimer Shows Luminescence and Sensitizes Photon Upconversion.

There has been much progress on mononuclear chromium(III) complexes featuring luminescence and photoredox activity, but dinuclear chromium(III) complexes have remained underexplored in these contexts until now. We identified a tridentate chelate ligand able to accommodate both meridional and facial coordination of chromium(III), to either access a mono- or a dinuclear chromium(III) complex depending on reaction conditions. This chelate ligand causes tetragonally distorted primary coordination spheres around chromium(III) in both complexes, entailing comparatively short excited-state lifetimes in the range of 400 to 800 ns in solution at room temperature and making photoluminescence essentially oxygen insensitive. The two chromium(III) ions in the dimer experience ferromagnetic exchange interactions that result in a high spin (S=3) ground state with a coupling constant of +9.3 cm-1. Photoinduced energy transfer from the luminescent ferromagnetically coupled dimer to an anthracene derivative results in sensitized triplet-triplet annihilation upconversion. Based on these proof-of-principle studies, dinuclear chromium(III) complexes seem attractive for the development of fundamentally new types of photophysics and photochemistry enabled by magnetic exchange interactions.

Ring Fusion Elevates the Electronic Mobility of Azabenzannulated Perylene Diimide.

The backwardness of n-type organic semiconductors still exists compared with the p-type counterparts. Thus, the development of high-performance n-type organic semiconductors is of great importance for organic electronic devices and their integrated circuits. In recent years, azabenzannulated perylene diimide (PDI), as one of immense bay-region-annulated PDI derivatives, has drawn considerable attentions. However, the electronic mobilities of azabenzannulated PDI derivatives are barely satisfactory. In this contribution, the peripheral benzene ring in azabenzannulated PDI 2 was fused to the ortho position by intramolecular C-H arylation cyclization. This endows the resultant azabenzannulated PDI 4 a planar configuration as well as electron deficient pentagonal ring. As a result, the electronic mobility of 4 is almost two orders of magnitude higher than that of the nonfused azabenzannulated PDI 2. This work shall pave a new avenue in elevating the performance of azabenzannulated PDI in organic electronics.

ATF5-regulated Mitochondrial Unfolded Protein Response Attenuates Neuronal Damage in Epileptic Rat by Reducing Endoplasmic Reticulum Stress Through Mitochondrial ROS.

Endoplasmic reticulum (ER) dysfunction caused by excessive ER stress is a crucial mechanism underlying seizures-induced neuronal injury. Studies have shown that mitochondrial reactive oxygen species (ROS) are closely related to ER stress, and our previous study showed that activating transcription factor 5 (ATF5)-regulated mitochondrial unfolded protein response (mtUPR) modulated mitochondrial ROS generation in a hippocampal neuronal culture model of seizures. However, the effects of ATF5-regulated mtUPR on ER stress and the underlying mechanisms remain uncertain in epilepsy. In this study, ATF5 upregulation by lentivirus infection attenuated seizures-induced neuronal damage and apoptosis in a rat model of pilocarpine-induced epilepsy, whereas ATF5 downregulation by lentivirus infection had the opposite effects. ATF5 upregulation potentiated mtUPR by increasing the expression of mitochondrial chaperone heat shock protein 60 (HSP60) and caseinolytic protease proteolytic subunit (ClpP) and reducing mitochondrial ROS generation in pilocarpine-induced seizures in rats. Additionally, upregulation of ATF5 reduced the expression of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), suggesting suppression of ER stress; Moreover, ATF5 upregulation attenuated apoptosis-related proteins such as B-cell lymphoma-2 (BCL2) downregulation, BCL2-associated X (BAX) and cleaved-caspase-3 upregulation. However, ATF5 downregulation exerted the opposite effects. Furthermore, pretreatment with the mitochondria-targeted antioxidant mito-TEMPO attenuated the harmful effects of ATF5 downregulation on ER stress and neuronal apoptosis by reducing mitochondrial ROS generation. Overall, our study suggested that ATF5-regulated mtUPR exerted neuroprotective effects against pilocarpine-induced seizures in rats and the underlying mechanisms might involve mitochondrial ROS-mediated ER stress.

LDLa containing C-type lectin mediates phagocytosis of V.anguillarum and regulates immune effector genes in shrimp.

C-type lectins (CTLs) function as pattern recognition receptors (PRRs) by recognizing invading microorganisms, thereby triggering downstream immune events against infected pathogens. In this study, a novel CTL containing a low-density lipoprotein receptor class A (LDLa) domain was obtained from Litopenaeus vannamei, designed as LvLDLalec. Stimulation by the bacterial pathogen Vibrio anguillarum (V. anguillarum) resulted in remarkable up-regulation of LvLDLalec, as well as release of LvLDLalec into hemolymph. The rLvLDLalec protein possessed broad-spectrum bacterial binding and agglutinating activities, as well as hemocyte attachment ability. Importantly, LvLDLalec facilitated the bacterial clearance in shrimp hemolymph and protected shrimp from bacterial infection. Further studies revealed that LvLDLalec promoted hemocytes phagocytosis against V. anguillarum and lysosomes were involved in the process. Meanwhile, LvLDLalec participated in humoral immunity through activating and inducing nuclear translocation of Dorsal to regulate phagocytosis-related genes and antimicrobial peptides (AMPs) genes, thereby accelerated the removal of invading pathogens in vivo and improved the survival rate of L. vannamei. These results unveil that LvLDLalec serves as a PRR participate in cellular and humoral immunity exerting opsonin activity to play vital roles in the immune regulatory system of L. vannamei.

Neonicotinoids Persisting in the Sea Pose a Potential Chronic Risk to Marine Organisms: A Case from Xiangshan Bay, China (2015-2019).

Neonicotinoid insecticides (neonics) are extensively employed in agriculture and pervade various environmental matrices. However, few studies have documented the occurrence and potential chronic ecological risks of these chemicals in the marine environment. We collected 720 seawater samples from Xiangshan Bay during 2015-2019 and the integrated concentrations of seven neonics were determined using the relative potency factor method. Trend analyses using the Mann-Kendall test in time series, along with the estimation of the flux of neonics into the sea, were conducted. At last, the ecological risk of neonics was evaluated by water quality criteria derivation based on species sensitivity distribution. Our findings revealed that 47.6% of samples contained at least one neonic, with the integrated concentration of neonics ranging from 63.30 to 1684.14 ng/L. Imidacloprid and dinotefuran exhibited the highest frequency of detection in the analysis. The significance level of the Mann-Kendall test ranged from 2.16 × 10-10 to 1.21 × 10-5 (S > 0), indicating all neonics behaved with sharply increasing trends. Approximately 8.47 × 10-2 tons of neonics were discharged into Xiangshan Bay. Notably, the integrated concentrations of neonics represented a potential chronic ecological risk to marine organisms. This study provided novel insights into the spatial distribution, source, and migration of neonic species and their impacts on marine ecosystems.

The Role of Human Adiponectin Receptor 1 in 2-Ethylhexyl Diphenyl Phosphate Induced Lipid Metabolic Disruption.

Epidemiological evidence links exposure to 2-ethylhexyl diphenyl phosphate (EHDPP) with lipid metabolic disruption, typically attributed to nuclear receptors, while the role of membrane receptors remains underexplored. This study explored the role of adiponectin receptor 1 (AdipoR1) in EHDPP-induced lipid metabolic disturbances. We examined EHDPP's binding affinity and transcriptional impact on AdipoR1. AdipoR1 knockdown (AdipoR1kd) human liver cells and coculture experiments with AdipoR1 activator (AdipoRon) were used to investigate the effect and the mechanism. EHDPP disrupted triglyceride and phospholipid synthesis and altered corresponding gene expression, mirroring effects in AdipoR1kd cells but diminishing in EHDPP-treated AdipoR1kd cells. RNA sequencing revealed that EHDPP primarily disrupted oxidative phosphorylation and insulin signaling dependent on AdipoR1. Mechanistically, EHDPP interacted with AdipoR1 and reduced AdipoR1 protein levels at 10-7 mol/L or higher, weakening the activation of the calmodulin dependent protein kinase ß (CaMKKß)/AMPK/acetyl CoA carboxylase pathway. Furthermore, EHDPP pretreatment blocked the increase in Ca2+ flux and the corresponding kinase CaMKKß, as well as liver kinase B1 (LKB1) activation induced by AdipoRon, which is necessary for AMPK activation. Collectively, these findings demonstrate that EHDPP-induced lipid imbalance is partially dependent on AdipoR1, expanding the understanding of environmental metabolic disruptors beyond nuclear receptors.

Helicobacter pylori induce circ_0046854 to regulate microRNA-511-3p/CSF1 axis and enhance the resistance of gastric cancer to cisplatin.

Helicobacter pylori (HP) is considered a major risk factor for gastric cancer (GC) and during this process, cytotoxin­associated gene A (CagA) plays in essence. The study mainly focused on the molecular mechanism of circular RNA 0046854 (circ_0046854) in HP-induced GC. Clinically, 56 cases of GC and normal tissues were collected, and the GC tissues were divided into HP-negative GC tissues (HP-) and 33 HP-positive GC tissues (HP+). Tissue expression of circ_0046854, microRNA (miR)-511-3p and colony-stimulating factor 1 (CSF1) was tested. BGC-823/Cisplatin (DDP) resistant strain was induced and cell growth and DDP resistance were detected after HP infection. In vivo experiments were performed using a mouse xenograft model. The relationship between circ_0046854, miR-511-3p and CSF1 was confirmed. GC tissues especially HP+ cancer tissues expressed high circ_0046854 and CSF1 and low miR-511-3p. HP-induced circ_0046854 expression in GC cells through CagA. Inhibition of circ_0046854 or miR-511-3p elevation inhibited the growth and DDP resistance in GC cells. Circ_0046854 acted as a sponge for miR-511-3p, which targeted CSF1. Restoring CSF1 could abolish the inhibitory effect of miR-511-3p overexpression on CagA+ HP-induced GC progression in vitro. Circ_0046854 silencing repressed tumor growth and aggrandized the inhibiting effects of DDP on tumorigenesis in vivo. Circ_0046854/miR-511-3p/CSF1 axis may be involved in the development of HP-induced GC, thus providing new ideas for studying the mechanism of HP-related gastric diseases.

CCR2 is a potential therapeutic target in peri-implantitis.

AIM: CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. MATERIALS AND METHODS: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. RESULTS: Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

Postnatal functional integrity of the brainstem auditory pathway in late preterm infants born of small-for-gestation age: how different from those born of appropriate-for-gestation.

It is unclear whether there is any postnatal abnormality in brainstem auditory function in late preterm small-for-gestational-age (SGA) infants. We investigated the functional integrity of the brainstem auditory pathway at 4 months after term in late preterm SGA infants and defined differences from appropriate-for-gestational age (AGA) infants. The maximum length sequence brainstem evoked response (MLS BAER) was recorded and analyzed in 24 SGA (birthweight < 3rd centile) infants and 28 AGA infants (birthweight > 10th centile). All infants were born at 33-36-week gestation without major perinatal and postnatal problems. We found that I-V interval in SGA infants was shorter than in AGA infants at higher click rates and significantly shorter at the highest rate of 910/s. Of the two smaller intervals, I-III interval was significantly shorter in SGA infants than in AGA infants at higher click rates of 455 and 910/s clicks, whereas III-V interval was similar in the two groups. The III-V/I-III interval ratio in SGA infants tended to be greater than in AGA infants at all rates and was significantly greater at 455 and 910/s clicks. The slope of I-III interval-rate functions in SGA infants was moderately smaller than in AGA infants.  Conclusions: The main and fundamental difference between late preterm SGA and AGA infants was a significant shortening in the MLS BAER I-III interval in SGA infants at higher click rates, suggesting moderately faster neural conduction in the caudal brainstem regions. Postnatal neural maturation in the caudal brainstem regions is moderately accelerated in late preterm SGA infants. What is Known: • At 40 weeks of postconceptional age, late preterm SGA infants manifested a mild delay in neural conduction in the auditory brainstem. What is New: • At 56 weeks of postconceptional age, late preterm SGA infants manifested moderately faster neural conduction in the caudal brainstem regions. • Postnatal neural maturation is moderately accelerated in the caudal brainstem regions of late preterm SGA infants.

Semisynthesis, Structure Elucidation and Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactones with Interesting Ketal Groups.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5' and C-6' on this compound's activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5' and C-6'. The R/S configuration of the diastereoisomer at C-13' was further determined through an NOE correlation analysis of CH3 or CH2 at the derivative C-13' position and the H-5' and H-6' by means of a 1D NOE experiment. Further comparative 1H NMR analysis of diastereoisomers showed the difference in the chemical shift (δ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15-24 and 28-35 demonstrated promising activity against M. marinum, with MIC90 values ranging from 70 to 90 µM, closely approaching the MIC90 of isoniazid. The preliminary structure-activity relationships showed that the ketal groups with aromatic rings at C-5' and C-6' could enhance the inhibition of M. marinum. Further study demonstrated that compounds 23, 24, 29, and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Clinical prediction models for knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To identify and describe existing models for predicting knee pain in patients with knee osteoarthritis. METHODS: The electronic databases PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library were searched from their inception to May 2023 for any studies to develop and validate a prediction model for predicting knee pain in patients with knee osteoarthritis. Two reviewers independently screened titles, abstracts, and full-text qualifications, and extracted data. Risk of bias was assessed using the PROBAST. Data extraction of eligible articles was extracted by a data extraction form based on CHARMS. The quality of evidence was graded according to GRADE. The results were summarized with descriptive statistics. RESULTS: The search identified 2693 records. Sixteen articles reporting on 26 prediction models were included targeting occurrence (n = 9), others (n = 7), progression (n = 5), persistent (n = 2), incident (n = 1), frequent (n = 1), and flares (n = 1) of knee pain. Most of the studies (94%) were at high risk of bias. Model discrimination was assessed by the AUROC ranging from 0.62 to 0.81. The most common predictors were age, BMI, gender, baseline pain, and joint space width. Only frequent knee pain had a moderate quality of evidence; all other types of knee pain had a low quality of evidence. CONCLUSION: There are many prediction models for knee pain in patients with knee osteoarthritis that do show promise. However, the clinical extensibility, applicability, and interpretability of predictive tools should be considered during model development.