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Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. METHODS: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. RESULTS: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p

Key message: Cd induces photosynthetic inhibition and oxidative stress damage in H. citrina, which mobilizes the antioxidant system and regulates the expression of corresponding genes to adapt to Cd and Pb stress. Cd and Pb are heavy metals that cause severe pollution and are highly hazardous to organisms. Physiological measurements and transcriptomic analysis were combined to investigate the effect of 5 mM Cd or Pb on Hemerocallis citrina Baroni. Cd significantly inhibited H. citrina growth, while Pb had a minimal impact. Both Cd and Pb suppressed the expression levels of key chlorophyll synthesis genes, resulting in decreased chlorophyll content. At the same time, Cd accelerated chlorophyll degradation. It reduced the maximum photochemical efficiency of photosystem (PS) II, damaging the oxygen-evolving complex and leading to thylakoid dissociation. In contrast, no such phenomena were observed under Pb stress. Cd also inhibited the Calvin cycle by down-regulating the expression of Rubisco and SBPase genes, ultimately disrupting the photosynthetic process. Cd impacted the light reaction processes by damaging the antenna proteins, PS II and PS I activities, and electron transfer rate, while the impact of Pb was weaker. Cd significantly increased reactive oxygen species and malondialdehyde accumulation, and inhibited the activities of antioxidant enzymes and the expression levels of the corresponding genes. However, H. citrina adapted to Pb stress by the recruitment of antioxidant enzymes and the up-regulation of their corresponding genes. In summary, Cd and Pb inhibited chlorophyll synthesis and hindered the light capture and electron transfer processes, with Cd exerting great toxicity than Pb. These results elucidate the physiological and molecular mechanisms by which H. citrina responds to Cd and Pb stress and provide a solid basis for the potential utilization of H. citrina in the greening of heavy metal-polluted lands. [ABSTRACT FROM AUTHOR]

The anomalous increases or deficits in the human body can be detected by the development of accurate and sensitive methods for metal quantification in low-level concentrations. Two digestion procedures have been tested on whole blood samples for use in inductively coupled plasma optical emission spectrometry trace metal analysis (ICP-OES). The two procedures are, (microwave digestion with nitric acid and hydrogen peroxide), and (simple dilution digestion with nitric acid, N-butanol, and Triton X-100). According to the findings, the overall recoveries of all determining metals for the microwave digestion were in the range of (96%) of the expected levels, whereas for simple dilution digestion they were in the range of (85–88%) of the expected levels. The results showed a significant difference in the recovery ratios in favor of lead (Pd) and cadmium (Cd) between simple dilution and microwave digestion procedures. The findings also show that the content of these metals may be reliably measured using simple dilution and microwave digestion procedures. Abbreviations: ICP-OES: Induction coupled optical emission spectroscopy; LOD: Limit of detection; LOQ: Limit quantification; AAPCC: American Association of Poison Control Centers; NAUSS: Naif Arab University for Security Sciences; %RSD: Relative standard deviation). [ABSTRACT FROM AUTHOR]

Background The management of inflammatory bowel disease [IBD] patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase [JAK] inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia. Methods All liver transplant recipients from the Australian states of Victoria, New South Wales, and Tasmania, who required tofacitinib or upadacitinib for the treatment of IBD, were identified using prospectively maintained liver transplant databases. Patients were followed up until medication cessation or last follow-up. Clinical safety and efficacy data were collected. Results Eight patients [median age 30 years] were included, seven of whom received first-line JAK inhibition with tofacitinib. All patients had failed one or more biologic therapies prior to commencing JAK inhibition, including six patients who had failed two or more agents. JAK inhibition was continued for a median of 17 months, with 143 patient-months of combined follow-up. The anti-rejection medication tacrolimus was prescribed in all patients. Overall, seven [88%] patients achieved clinical remission, including all three patients who were switched from tofacitinib to upadacitinib. One patient required colectomy after 1 month of treatment. There were no other cases of serious infection, venous thromboembolism, or major adverse cardiovascular events during follow-up. Conclusions As the largest case series to date, these data indicate that combining JAK inhibition with transplant anti-rejection medication may be a safe and clinically effective method of treating IBD in patients with prior biologic failure. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloproteinase domain 10 (ADAM10), a member of the ADAM family, is a cellular surface protein with potential adhesion and protease/convertase functions. The expression regulations in cancers by natural products [adenosine (AD) and its analogs, cordycepin (CD), and N6, N6-dimethyladenosine (m6A)], and immune regulation are unclear. As results, AD, CD, and m2A inhibited ADAM10 expression in various cancer cell lines, indicating their roles in anti-cancer agents. Further molecular docking with ADAM10 protein found the binding energies of all docking groups were <-7 kcal/mol for all small-molecules (AD, CD and m62A), suggesting very good binding activities. In addition, analysis of the immunomodulatory roles in cancer showed that ADAM10 was negatively correlated with immunomodulatory genes such as CCL27, CCL14, CCL25, CXCR5, HLA-B, HLA-DOB1, LAG3, TNFRSF18, and TNFRSF4 in bladder urothelial carcinoma, thymoma, breast invasive carcinoma, TGCT, kidney renal papillary cell carcinoma, SKCM and thyroid carcinoma, indicating the immune-promoting roles for ADAM10. LAG3 mRNA levels were reduced by both AD and CD in vivo. ADAM10 is also negatively associated with tumor immunosuppression and interrelated with the immune infiltration of tumors. Overall, the present study determined ADAM10 expression by AD, CD and m62A, and in AD or CD/ADAM10/LAG3 signaling in cancers, and suggested a potential method for immunotherapy of cancers by targeting ADAM10 using the small molecules AD, CD and m62A, and in AD or CD/ADAM10/LAG3 signaling in cancers, and suggested a potential method for immunotherapy of cancers by targeting ADAM10 using the small molecules AD, CD and m62A. [ABSTRACT FROM AUTHOR]

In Paper-I, we developed a two-phase model to connect dynamically hot galaxies (such as ellipticals and bulges) with the formation of self-gravitating gas clouds (SGCs) associated with the fast assembly of dark matter haloes. Here, we explore the implications of the model for the size–stellar mass relation of dynamically hot galaxies. Star-forming sub-clouds resulting from the fragmentation of the turbulent SGC inherit its spatial structure and dynamical hotness, producing a 'homologous' relation, |$r_{\rm f}\approx \, 100\, r_{\rm bulge}$|⁠ , between the size of a dynamically hot galaxy (⁠|$r_{\rm bulge}$|⁠) and that of its host halo assembled in the fast regime (⁠|$r_{\rm f}$|⁠), independent of redshift and halo mass. This relation is preserved by the 'dry' expansion driven by dynamical heating when a galaxy becomes gas-poor due to inefficient cooling, and is frozen due to the stop of bulge growth during the slow assembly regime of the halo. The size–stellar mass relation is thus a simple combination of the galaxy–halo homology and the non-linear stellar mass–halo mass relation. Using a set of halo assembly histories, we reproduce all properties in the observed size–mass relation of dynamically hot galaxies, including the flattening in the low-mass end and the upturn in the massive end. The prediction matches observational data currently available to |$z \approx 4$|⁠ , and can be tested in the future at higher z. Our results indicate that the sizes of dynamically hot galaxies are produced by the dissipation and collapse of gas in haloes to establish SGCs in which stars form. [ABSTRACT FROM AUTHOR]

The relation between nuclear star clusters (NSCs) and the growth of the central supermassive black holes (SMBHs), as well as their connection to the properties of the host galaxies, is crucial for understanding the evolution of galaxies. Recent observations have revealed that about 10 per cent of nucleated galaxies host hybrid nuclei, consisting of both NSCs and accreting SMBHs that power active galactic nuclei (AGNs). Motivated by the potential of the recently published multiwavelength data sets from LeMMINGs survey, here we present the most thorough investigation to date of the incidence of hybrid nuclei in a large sample of 100 nearby nucleated galaxies (10 E, 25 S0, 63 S, and 2 Irr), covering a wide range in stellar mass (⁠|$M_{*,\rm gal} \sim 10^{8.7}-10^{12}~\rm M_{\odot }$|⁠). We identify the nuclei and derive their properties by performing detailed 1D and 2D multicomponent decompositions of the optical and near-infrared HST stellar light distributions of the galaxies using Sérsic and core-Sérsic models. Our AGN diagnostics are based on homogeneously derived nuclear 1.5 GHz e -MERLIN radio, Chandra X-ray (0.3–10 keV), and optical emission-line data. We determine the nucleation fraction (⁠|$f_{\rm nuc}$|⁠) as the relative incidence of nuclei across the LeMMINGs HST sample and find |$f_{\rm nuc} =~$| 100/149 (= 67 |$\pm$| 7 per cent), confirming previous work, with a peak value of |$49/56~(= 88 \pm 13$|  per cent) at bulge masses |$M_{*,\rm bulge}\sim 10^{9.4}- 10^{10.8}~ \rm M_{\odot }$|⁠. We identify 30 nucleated LeMMINGs galaxies that are optically active, radio-detected, and X-ray luminous (⁠|$L_\textnormal {X} \gt 10^{39}$| erg s |$^{-1}$|⁠). This indicates that our nucleated sample has a lower limit |$\sim$| 30 per cent occupancy of hybrid nuclei, which is a function of |$M_{*,\rm bulge}$| and |$M_{*,\rm gal}$|⁠. We find that hybrid nuclei have a number density of |$(1.5 \pm 0.4)\times 10^{-5}$|  Mpc |$^{-3}$|⁠ , are more common at |$M_{*,\rm gal}\sim 10^{10.6}- 10^{11.8}~\rm M_{\odot }$| and occur, at least, three times more frequently than previously reported. [ABSTRACT FROM AUTHOR]

A three-year pot experiment was designed to investigate cadmium (Cd) accumulation in the various parts of poplar (Populus deltoides Bartr. cv. ‘Lux’ I-69/55) by setting up 5 Cd application treatments (0, 5, 20, 50, and 100 mg/kg dry soil). The results showed that poplar exhibited a high tolerance to Cd stress, with Cd uptake significantly increasing across all plant parts as soil Cd levels rose. In general, leaves exhibited the highest Cd concentration while stems had the lowest. An upward increase trend of the accumulation of Cd in the aboveground parts from the base wood, along the stem to the branch, until the leaves, as well as a radially outward increase of Cd from the wood near the pith, to the wood near the bark, and finally to the bark, were observed. Over the three successive years, poplar trees exhibited a generally increasing extraction ability in terms of Cd concentration and the bioconcentration factor (BCF) in their aboveground parts, attributed to the enhanced leaf transpiration and conducting tissue development. The BCFs of various parts of poplar ranged from 0.09 to 6.30, following the trend of leaf > bark > branch > root > stem. [ABSTRACT FROM AUTHOR]

Nano-sized biochar, which is a small structure prepared from biochar by grinding, has surpassed traditional biochar in performance, showing enhanced effects and potential for a wide range of environmental applications. Firstly, this paper visualizes and analyzes the literature in this field by CiteSpace to clarify the development trend of nano-sized biochar. The review intuitively shows the most influential countries, the most productive institutions, and the most concerned hot spots in the field of nano-sized biochar. Secondly, these hotspots in environment management are summarized by keywords and clustering: (1) The application of ball milling is a modification scheme that researchers have paid attention to, and it is also a key method for preparing biochar nanomaterials. It has a more dispersed structure and can support more modified materials. (2) Nano-sized biochar in the comprehensive utilization of water, soil, and plants was discussed and is a small range of application modification methods. (3) The bidirectional effects of nano-sized biochar on plants were analyzed, and the challenges in its application were listed. Finally, the economic management of nano-sized biochar and the relationship between microorganisms are the focus of the next research. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease that involves modified low-density lipoproteins (LDL) which play a pivotal role in the initiation and progression of the disease. Myeloperoxidase oxidized LDL (Mox-LDL) is considered to be the most patho-physiologically relevant type of modified LDL and has been reported to be ubiquitously present in atheroma plaques of patients with atherosclerosis. Besides its involvement in the latter disease state, Mox-LDL has also been shown to be implicated in the pathogenesis of various illnesses including sleep disorders, which are in turn associated with heart disease and depression in many intricate ways. Meanwhile, we have recently shown that lox-1-mediated Mox-LDL signaling modulates neuroserpin activity in endothelial cells, which could have major implications that go beyond the pathophysiology of stroke and cerebrovascular disease (CD). Of note is that tissue plasminogen activator (tPA), which is the main target of neuroserpin in the brain, has a crucial function in the processing of brain-derived neurotrophic factor (BDNF) into its mature form. This factor is known to be involved in major depressive disorder (MDD) development and pathogenesis. Since tPA is more conventionally recognized as being involved in fibrinolytic mechanisms, and its effect on the BDNF system in the context of MDD is still not extensively studied, we speculate that any Mox-LDL-driven change in the activity of tPA in patients with atherosclerosis may lead to a decrease in the production of mature BDNF, resulting in impaired neural plasticity and depression. Deciphering the mechanisms of interaction between those factors could help in better understanding the potentially overlapping pathological mechanisms that regulate disease processes in CD and MDD, supporting the possibility of novel and common therapeutic opportunities for millions of patients worldwide. [ABSTRACT FROM AUTHOR]

Odd radio circles (ORCs) are mysterious rings of faint, diffuse emission recently discovered in radio surveys, some of which may be associated with galaxies in relatively dense environments. We propose that such ORCs are synchrotron emission from remnants of explosive galactic outflows, calling them OGREs, and discuss their broad-band non-thermal emission and evolution. We posit that a large amount of energy was ejected from the central galaxy in the past, creating an outgoing shock that accelerates cosmic rays. Assuming plausible values for the density, temperature and magnetic field of the ambient medium, consistency with the observed spectral index, size, and power of the ORCs requires the energy to be as high as ∼1060 erg, suggesting that their sources could be active galactic nuclei. We calculate the spectral energy distributions (SEDs) of the OGREs and their evolution, including synchrotron, inverse Compton (IC), and bremsstrahlung emission from electrons, and pion-decay emission from protons. We find that the SEDs of the younger OGREs are not greatly different from those of older ones currently observable as ORCs if radiative cooling of electrons is effective. As such younger OGREs are expected to be rarer and smaller, they may not be readily observable. However, if radiative cooling of electrons is ineffective, younger OGREs may be detectable in X-rays. [ABSTRACT FROM AUTHOR]

One of the most popular applications of nanotechnology in both topical and internal medicine administration to the body is nanogel technology. The materials comprising the nanoparticulate frameworks are less than 100 nm in a single measurement. The goal of this review paper is to provide a concise overview of the most recent developments in the nanogel medicine delivery framework with regard to drug loading and swelling. It categorises according to links (chemical and physical) and responding behaviour. This article is to give a broad overview of nanogels, their innovative use in many contexts, and current synthesis techniques. NGs use drugs for a variety of reasons, including diagnostics, gene targeting, organ targeting, and many more. Different pulmonary, nasal, transdermal, intra-ocular, oral, and parenteral routes can be used to give NGs. The primary goals of this review are to present broad details on NGs, their characteristics, multiple categories, medication targeting strategies, kinds of drug delivery systems, assessment techniques, and cutting-edge uses for NGs in depth. [ABSTRACT FROM AUTHOR]

Background: A significant limitation of mucosal healing as a treatment target in Crohn’s disease is that Ileocolonoscopy remains the gold-standard for assessing disease activity. Identification of optimal biomarkers and their cut-off values is an unmet need in the context of tight monitoring strategy. Aim of work: To study the performance of Fecal lactoferrin in patients with Crohn’s disease in comparison to endoscopic assessment, clinical indices and fecal calprotectin to address whether it correlates with endoscopic severity of inflammation and whether it could be used as reliable surrogate marker of endoscopically detected mucosal healing after therapy. Methods: In this prospective study, 35 patients with active Crohn’s disease were recruited. All patients provided stool samples for lactoferrin and calprotectin at baseline and underwent colonoscopy. Twentysix (26) of these patients were followed up after 6-9 months of therapy initiation or upgrade. Fecal lactoferrin was compared with the simple endoscopic score of Crohn’s disease (SES-CD), Harvey-Bradshaw index (HBI) and fecal calprotectin. Data was then analyzed to identify cut-off levels to detect endoscopic response/remission. Results: Lactoferrin showed excellent performance in detecting remission (AUC 0.93) with a sensitivity of 85.7% and a specificity of 88.9% at a cut-off value of 21.5µg/g. A drop of more than 26.2% from baseline values is 100% sensitive and specific in detecting endoscopic response (≥50% reduction from baseline SES-CD). Lactoferrin showed a strong correlation with SES-CD (r=0.74) and calprotectin (r=0.91) Conclusion: Fecal lactoferrin is a reliable marker of response to therapy and mucosal healing, making endoscopic monitoring of treatment success less necessary. Whether lactoferrin is superior to calprotectin or not would require further investigation. [ABSTRACT FROM AUTHOR]

The karst area has become a high-risk area for Cadmium (Cd) exposure. Interestingly, the high levels of Cd in soils do not result in an excessive bioaccumulation of Cd in rice. Carbonate rock dissolution ions (CRIs) could limit the accumulation and translocation of Cd in rice. CRIs can become a major bottleneck in the remediation and management of farmlands in karst areas. However, there is limited research on the effects of CRIs in soils on Cd accumulation in rice. The karst area of lime soil (LS) and the non-karst areas of yellow soil (YS) were collected, and an external Cd was added to conduct rice cultivation experiments. Cd and CRIs (Ca2+, Mg2+, CO32−/HCO3−, and OH−) in the rice–soil system were investigated from the grain-filling to maturity periods. The results showed that CRIs of LS were significantly higher than that of YS in different treatments. CRIs of LS were 2.05 mg·kg−1 for Ca2+, 0.90 mg·kg−1 for Mg2+, and 42.29 mg·kg−1 for CO32− in LS. CRIs could influence DTPA Cd, resulting in DTPA Cd of LS being lower than that of YS. DTPA Cd of YS was one to three times larger than that of YS. Cd content in different parts of rice in YS was higher than that of LS. Cd in rice grains of YS was one to six times larger than that of LS. The uptake of Cd from the soil during Filling III was critical in determining rice Cd accumulation. CRIs in the soil could affect Cd accumulation in rice. Ca2+ and Mg2+ had significant negative effects on Cd accumulation of rice at maturity and filling, respectively. CO32−/HCO3− and OH− had significant negative effects on DTPA Cd in soil. [ABSTRACT FROM AUTHOR]

Biodiversity commonly contributes to ecosystem functioning and provides ecosystem services. Biochar application is frequently used to remediate soils contaminated with heavy metals. As many invasive plant species can quickly form huge amounts of biomass, they are potentially useful for producing biochar for remediating contaminated soils. However, it remains untested whether invasive species richness contributes to biochar-mediated soil remediation. We applied single biochar made from each of six invasive plant species and biochar mixtures (i.e., mixtures of biochar derived from 2, 3, and 6 invasive plant species) to soils contaminated with cadmium (Cd), with no biochar application as the control. We then grew native plant communities on these soils. Compared to the control, biochar application significantly decreased Cd bioavailability (− 34% averaged across the three richness treatments) in the soils, and this effect increased with increasing invasive species richness involved in the biochar mixtures (from − 22 to − 38%). Biochar application significantly increased both the concentration (+ 126%) and pool size (+ 59%) of Cd in roots of the native plant community, although it significantly decreased its biomass (− 25%). Thus, invasive species diversity can contribute to biochar-mediated remediation of soils contaminated with Cd. Our findings indicate a novel biodiversity-mediated ecosystem service, i.e., the use of multiple invasive plant species for the production of biochar. As harvesting of invasive species for biochar production may also contribute to their management, this might mitigate the two ecological problems at once. [ABSTRACT FROM AUTHOR]

This research aimed to examine the compound effects of polyacrylamide (PAM) and cadmium (Cd) on plant growth subsequent to the mixing of municipal sludge with soil and to explore the potential ecological risks associated with the use of sludge. A pot experiment was performed wherein four gradients (0, 5, 15, and 20 g/[kg dry sludge]) were established corresponding to different PAM concentrations to assess the effects on the physiological and biochemical parameters of Brassica campestris L. ssp. chinensis Makino and Brassica campestris L. and the effects on Cd and PAM concentrations in soil. The findings indicated that the biomass of both plants increased when the total PAM concentration ranged from 5 g to 15 g/(kg dry sludge). Concurrently, polyacrylamide (PAM) downplayed the uptake of Cd by the plants, reduced phytotoxicity, and increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and peroxidase (POD) in the roots. However, the biomass of Brassica campestris L. ssp. chinensis Makino and Brassica campestris L. decreased significantly when the total PAM concentration was exceeded 15 g/(kg dry sludge), and the toxic effect of Cd on pants was enhanced to some extent. Especially when the PAM concentration was 20 g/(kg dry sludge), apparent cell damage was observed in root cells. It was further noted that Brassica campestris L. portrayed a higher tolerance towards higher proportions of sludge compared with Brassica campestris L. ssp. chinensis Makino. Sludge holds a wider scale of applicability in landscaping than in agriculture. A fusion of polyacrylamide (PAM) and antioxidant enzymes could potentially counteract the effects of Cd within a specific concentration range, serving as a defense mechanism against stress. The data obtained from this study are crucial for unraveling anti‐stress responses and detoxification mechanisms employed by different plant species under the influence of factors such as PAM, Cd, and others, thus providing novel insights into research related to land use involving sludges. [ABSTRACT FROM AUTHOR]

Observations of nearby massive galaxies have revealed that they are older and richer in metals and magnesium than their low-mass counterparts. In particular, the overabundance of magnesium compared to iron, [Mg/Fe], is interpreted to reflect the short star formation history that the current massive galaxies underwent early in the Universe. We present a systematic revision of the [Mg/Fe] – velocity dispersion (σ) relation based on stacked spectra of early-type galaxies with a high signal-to-noise ratio from the Sloan Digital Sky Survey. Using the penalized pixel-fitting (pPXF) method and the MILES single stellar population models, we fit a wide optical wavelength range to measure the net α-abundance. The combination of pPXF and α-enhanced MILES models incorrectly leads to an apparently decreasing trend of [α/Fe] with velocity dispersion. We interpret this result as a consequence of variations in the individual abundances of the different α-elements. This warrants caution for a naive use of full spectral fitting algorithms paired with stellar population models that do not take individual elemental abundance variations into account, especially when deriving averaged quantities such as the mean [α/Fe] of a stellar population. In addition, and based on line-strength measurements, we quantify the impact of a non-universal initial mass function on the recovered abundance pattern of galaxies. In particular, we find that a simultaneous fit of the slope of the initial mass function and the [Mg/Fe] results in a shallower [Mg/Fe]–σ relation. Therefore, our results suggest that star formation in massive galaxies lasted longer than what has been reported previously, although it still occurred significantly faster than in the solar neighbourhood. [ABSTRACT FROM AUTHOR]

We present new H- and K-band spectroscopy for the bulge of M31, taken with the LUCI spectrograph at the Large Binocular Telescope (LBT). We studied radial trends of CO absorption features (namely, CO1.58, CO1.60, CO1.64, CO1.66, CO1.68, CO2.30, CO2.32, and CO2.35) in the bulge of M31, out to a galactocentric distance of ∼100″ (∼380 pc). We find that most COs do not exhibit a strong radial gradient, despite the strong metallicity gradient inferred from the optical spectral range, except for CO1.64, showing a steep increase in the center. We compared the observed line strengths to predictions of different state-of-the-art stellar population models, including an updated version of EMILES models, which also uses the extended IRTF spectral library. The observed COs are close to models' predictions, but in some models they turn out to be underestimated. We find that the lack of radial gradients is due to the combination of increasing CO strength with metallicity and C abundance, and decreasing CO strength with IMF slope and O abundance. We speculate that the steep gradient of CO1.64 might be due to Na overabundance. Remarkably, we were able to fit, at the same time, optical indices and all the NIR COs (except for CO1.68), leaving abundance ratios (i.e., [C/Fe], [O/Fe], and [Mg/Fe]) as free-fitting parameters, imposing age and metallicity constraints from the optical spectral range, with no significant contribution from intermediate-age populations (∼1 Gyr-old). For the majority of the bulge, we find [Mg/Fe] ∼ 0.15 dex, [O/Fe] larger than [Mg/Fe] (by ∼0.1 dex), and C abundance consistent with that of Mg. In the central (few arcsec) region, we still find an enhancement of O and Mg, but significantly lower [C/Fe]. We find that the COs' line strengths of the bulge are significantly lower than those of massive galaxies, possibly because of a difference in carbon abundance, as well as, to some extent, total metallicity. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn's disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD. [ABSTRACT FROM AUTHOR]

Low bone mineral density (BMD) is common in adults with coeliac disease (CD), even in individuals adhering to a gluten-free diet (GFD). Women are more likely to have low BMD and have an increased risk of osteoporosis, so women with pre-existing low BMD related to CD are at an even higher risk. BMD assessed by dual X-ray absorptiometry (DXA) and bone quality assessed through quantitative ultrasound (QUS) were investigated in 31 premenopausal women with CD consuming a GFD, and 39 matched healthy controls from the Lower North Island, New Zealand. In addition, bone metabolism and nutrient status were assessed, and four-day diet diaries were used to estimate nutrient intake. No statistically significant differences were found in BMD assessed by DXA between the two groups at the hip, lumbar spine or forearm. However, the parameters measured by the QUS were significantly lower in CD participants. Dietary data indicated significantly lower intakes of energy, dietary fibre, magnesium and phosphorus in women with CD, likely as a result of a reduced intake of wholegrain foods, and suggested that both groups had inadequate intake of calcium. No significant differences were demonstrated in biochemical parameters. BMD and bone biomarkers indicated no differences between coeliac and healthy women in New Zealand. However, these findings suggest that QUS may be more sensitive for the coeliac population, due to the disease's affect on the trabecular bone, and warrant further research. [ABSTRACT FROM AUTHOR]

To verify the remediation effects of different soil conditioners on lightly Cd-contaminated paddy fields, field plot experiments were conducted in 2021 and 2022 in Daye City, Hubei Province. The effects of 20 soil conditioners on rice yield, brown rice Cd contents, soil pH, and soil available Cd contents were studied. The results showed that compared with the control group, the rice yield changed from - 9.80% to 20.09%, the Cd reduction rate of brown rice was 8.05% to 79.57%, the soil pH increased by - 0.01 to 1.13 units, and the available Cd contents decreased by 4.79% to 25.00%. There was a significant negative correlation between soil pH value and available Cd content for two consecutive years. Meantime, four representative conditioning agents (organic: P3, P4, inorganic: P11, P12) in 2021 were further selected to explore their effects on the transfer and accumulation of Cd in soil-plant and the transformation of five types of occurrence forms in soil. In 2021, the transport coefficient of Cd from soil to root of rice were significantly decreased by all four treatments, and the effect of inorganic conditioners (P11, P12) were significantly better than that of organic conditioners (P3, P4) . The proportion of exchangeable Cd and carbonate-bound Cd in soil decreased by 5.91–17.77 percentage points and 6.33–8.88 percentage points, respectively, under the treatment of various conditioners (P3, P4, P11, P12) . The proportion of Fe-Mn bound Cd, organically bound Cd and residual Cd in soil were increased by 3.47–16.31, 0.80-6.50 percentage points and 4.82–7.05 percentage points, respectively. Organic conditioners (P3, P4) tend to convert soil Cd to organically bound Cd, while inorganic conditioners (P11, P12) tend to convert soil Cd to Fe-Mn bound Cd. Overall, two years of field experiments showed that the selection of suitable conditioners could realize the safe utilization of Cd-polluted farmland, and P12 conditioner (CaO≥28%) was recommended as the conditioner for the remediation of mild Cd pollution in Daye City, Hubei Province. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) pollution is a serious threat to food safety and human health. Minimizing Cd uptake and enhancing Cd tolerance in plants are vital to improve crop yield and reduce hazardous effects to humans. In this study, we designed three Cd concentration stress treatments (Cd1: 0.20 mg·kg−1, Cd2: 0.60 mg·kg−1, and Cd3: 1.60 mg·kg−1) and two foliar silicon (Si) treatments (CK: no spraying of any material, and Si: foliar Si spraying) to conduct pot experiments on soil Cd stress. The results showed that spraying Si on the leaves reduced the Cd content in brown rice by 4.79–42.14%. Si application increased net photosynthetic rate (Pn) by 1.77–4.08%, stomatal conductance (Gs) by 5.27–23.43%, transpiration rate (Tr) by 2.99–20.50% and intercellular carbon dioxide (CO2) concentration (Ci) by 6.55–8.84%. Foliar spraying of Si significantly increased the activities of superoxide dismutase (SOD) and peroxidase (POD) in rice leaves by 9.84–14.09% and 4.69–53.09%, respectively, and reduced the content of malondialdehyde (MDA) by 7.83–48.72%. In summary, foliar Si spraying protects the photosynthesis and antioxidant system of rice canopy leaves, and is an effective method to reduce the Cd content in brown rice. [ABSTRACT FROM AUTHOR]

Background: Evidence has shown that the individual metrics in Life's Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD). We also tested whether genetic susceptibility could modify these associations. Methods: A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0–49), moderate CVH (50–79), and high CVH (80–100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status. Results: Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20–0.45; CD: 0.33, 95% CI: 0.20–0.57) was observed in participants with both high CVH and low genetic risk. Conclusions: Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD. [ABSTRACT FROM AUTHOR]

Objective: The study aims to assess how oral misoprostol for cervical ripening affects the time of cesarean delivery (CD) for fetal heart rate (FHR) abnormalities in pre‐eclampsia patients. Secondary goals include determining the role of uterine hyperstimulation, comparing misoprostol with Foley catheter, and identifying risk factors for FHR abnormalities associated with CD. Methods: A previously published randomized clinical trial was subjected to a secondary analysis (NCT01801410). We conducted a time‐dependent analysis, stratifying the population based on the final mode of induction used (low‐dose oral misoprostol vs Foley catheter). Results: There was no CD for FHR abnormalities within 2 h of starting misoprostol. At 5 h, the cumulative incidence of CD for FHR abnormalities in the misoprostol group was 2.10%, while it was 1.00% in the Foley group (P = 0.565). After 25 h, the CD risk for FHR abnormalities remained constant in both groups at 21.00% (95% confidence interval [CI] 15.00%–28.00%). Within 5 h of misoprostol induction, the risk of uterine hyperstimulation was similar in both groups (0.33% in misoprostol vs 0.34% in Foley group, P = 0.161). The risk of CD for FHR abnormalities was unaffected by newborn weight centiles. Conclusion: There was no significant difference in CD risk for FHR abnormalities between misoprostol and Foley catheter induction. Nonetheless, the cumulative incidence of CD for FHR abnormalities increased faster in the misoprostol group, indicating that FHR monitoring timing should be tailored to the induction method. Synopsis: The incidence of cesarean delivery for fetal heart anomalies increased faster in the misoprostol group than in Foley group, and for that reason tailoring fetal monitoring timing to induction method is critical. [ABSTRACT FROM AUTHOR]

Pinus thunbergii and Euonymus japonicus are two species commonly found in arid and semi-arid areas; however, their responses in terms of physiological traits and soil properties under drought and cadmium (Cd) stress are not clear. In this study, we carried out single and combined stress treatments consisting of drought and Cd on saplings of P. thunbergii and E. japonicus and investigated the responses in terms of the physiological traits and soil properties of both species. For both species, under single Cd stress, Cd was observed in both the xylem and phloem, while the root Cd2+ flow rate fluctuated at different levels of Cd stress. Under both single and combined stress, as the stress level increased, the abscisic acid (ABA) content of the leaves and roots increased significantly, while the indole-3-acetic acid (IAA) content of the leaves and roots decreased significantly. Moreover, the non-structural carbohydrate (NSC) content of the leaves, stems, and roots, as well as the leaf chlorophyll content, decreased significantly. Under drought stress, the xylem water potential and hydraulic conductivity significantly decreased, which was exacerbated by Cd stress; this led to a more significant decrease in water potential and hydraulic conductivity under the combined stresses. Meanwhile, no significant changes in the conduit lumen diameter and double-wall thickness were observed, except for the double cell wall thickness of the P. thunbergii tracheid, which increased. In addition, both the single stresses and the combined stress of drought and Cd induced significant changes in the soil properties of the two species, i.e., the ammonium nitrogen, nitrate nitrogen, and effective phosphorus of the soil increased significantly, and the increase in content was more significant under combined stress. The diversity of the soil microbial community of P. thunbergii saplings significantly increased, while no change was found in its microbial community abundance under the single stresses and combined stress; however, the diversity and abundance of the soil microbial community in E. japonicus saplings showed the opposite pattern, which indicates that the effect of Cd on soil microorganisms is more significant than the effect of drought. The activity of sucrase and catalase in P. thunbergii soil fluctuated under the single stress and combined stress when compared, and the activity of sucrase in the soil of the E. japonicus species decreased. However, its catalase activity increased significantly under the single drought and Cd stress and combined stress when compared. We found that the combined stresses exacerbated the effects of the single stress in both species. Our study provides more detailed information on the responses in terms of the physiological traits and soil properties of the two species under single and combined stress consisting of drought and Cd. [ABSTRACT FROM AUTHOR]

Areas contaminated with cadmium require remediation because it is a highly toxic element. The aim of this study was to assess the Cd tolerance of four grass species (Poa pratensis, Lolium perenne, Festuca rubra, and Festuca pratensis) and to identify the most useful grass for the phytostabilization of areas with extremely high Cd content in the soil. Additionally, the relationship between grass tolerance to Cd and the glutathione (GSH) content in shoots was examined. Two series of pot experiments were carried out using soil artificially contaminated with Cd. Three levels of contamination were used—30, 60, and 130 mg kg−1 Cd—against a control. The plants were cut down 2 months after sowing. At the Cd1 level, L. perenne showed the highest tolerance to Cd (tolerance index TI = 86), while P. pratensis had the lowest tolerance (TI = 65). At Cd2, the TIs ranged from 52 to 59, indicating a similar tolerance of all species. Cd3 was most harmful to L. perenne (TI = 24), while P. pratensis was the most tolerant (TI = 31). Grassroots accumulated much more Cd than shoots. L. perenne showed the greatest increase in root Cd at each contamination level, followed by F. pratensis and then P. pratensis and F. rubra. It is noteworthy that the tolerance of grasses to Cd3 was related to the GSH content in shoots. P. pratensis and F. rubra increased the GSH content 4.6 and 3.6 times, respectively, while L. perenne and F. pratensis only increased it 2.3 times compared to the control plants. [ABSTRACT FROM AUTHOR]

In order to analyse the impact of biochar in terms of reducing the bioavailability of cadmium (Cd) in soil, a study was conducted on the solidification effect of biochar on soil cadmium and its resistance to cadmium contamination in lettuce. In this study, soil which was contaminated with 10 mg/kg cadmium was used as the substrate; corn, rice, and wheat straw biochar were used as solidification and amendment materials; and lettuce (Lactuca sativa L. cv. Grand Rapids) was used as the test plant. The morphological characteristics of the biochar, soil pH, electrical conductivity, cation exchange capacity, and soil-available Cd, as well as lettuce plant height, fresh weight, and leaf Cd content, were measured and analysed. The results showed that all three types of biochar possessed distinct porous structures and functional groups such as hydroxyl, ether, and carbonyl groups. Increases in soil pH, electrical conductivity (EC), cation exchange capacity (CEC), lettuce plant height, and fresh weight were effectively promoted. Additionally, a significant reduction in the available Cd content in the soil and Cd content in lettuce leaves was observed, with the inhibitory effect becoming more pronounced as the biochar application rate increased. When 5% corn straw biochar was added (1 kg of substrate with 50 g of biochar), the best inhibitory effect on Cd contamination was observed, with a cadmium content of 4.63 mg/kg in lettuce leaves. The available Cd in the soil and the Cd content in lettuce leaves decreased by 32.00% and 49.78%, respectively, compared to the CK group (without biochar treatment). Additionally, the plant height and fresh weight of lettuce increased by 25.56% and 31.31%, respectively, compared to the CK group. This indicated that the application of straw biochar can stabilise soil Cd, reduce the availability of Cd in the soil, inhibit the transfer of Cd into lettuce, promote the growth of lettuce, and lower the ecological environmental risk of Cd. These research results can provide a theoretical basis and scientific guidance for the remediation of soil Cd contamination and the safe production of lettuce. [ABSTRACT FROM AUTHOR]

Biochar and nanoparticles (NPs) are potential strategies for increasing plant yield and minimizing the negative effects of toxic metals on sweet basil (Ocimum basilicum L). The current study aims to reduce the access of toxic elements to the oil extracted from basil plants growing in polluted soils by biochar and NPS of silicon (Si) and boron (B). Sweet basil plants were grown in contaminated soil that contained cadmium (Cd) and lead (Pb) at concentrations of 58 and 800 mg kg−1, respectively. The experiment included two doses of biochar (0 and 1%, w/w) and four foliar combinations of Si and B nanoparticles at the dose of 100 mg L−1 of Si and/or B. Cd and Pb availability were reduced by 44 and 48%, respectively, compared to the control. The soil pH raised significantly (p < 0.05) as a result of biochar addition. Furthermore, biochar addition at the dose of 1%, (w/w) caused a 14% increase in the soil organic matter. The highest growth parameters of basil plants were obtained from the biochar treatment with Si + B NPs foliar application. The treatment that was amended with biochar and sprayed with Si + B showed the greatest significant values of nitrogen (N), phosphorus (P), potassium (K), and calcium (Ca) content in basil plants. The chlorophyll content of basil leaves rose along with the synthesis of proline and soluble carbohydrates after the addition of biochar to the polluted soil and Si + B spraying. Biochar minimized Cd in the leaf and oil by 48 and 49%, respectively, compared to the control, while Pb concentrations were reduced by 29 and 49%, respectively. The oil extracted from the basil plants grown in the soil amended with biochar contained 50–52 and 23–26 μg kg−1 of Cd and Pb, respectively. Adding biochar to the contaminated soil increases the oil yield of sweet basil and reduces its content of toxic elements, while spraying the basil plant with silicon and boron nanoparticles increases the plant's resistance to metal toxicity. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that alterations in the gut microbiome impact the development of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD often requires the use of immunosuppressant drugs and biologic therapies to facilitate clinical remission and mucosal healing, some patients do not benefit from these drugs, and the reasons for this remain poorly understood. Despite advancements, there is still a need to develop biomarkers to help predict prognosis and guide treatment decisions. The aim of this study was to investigate the gut microbiome of IBD patients using biologics to identify microbial signatures associated with responses, following standard accepted criteria. Microbiomes in 66 stool samples from 39 IBD patients, comprising 20 CD and 19 UC patients starting biologic therapies, and 29 samples from healthy controls (HCs) were prospectively analyzed via NGS and an ensemble of metagenomics analysis tools. At baseline, differences were observed in alpha and beta metrics among patients with CD, UC and HC, as well as between the CD and UC groups. The degree of dysbiosis was more pronounced in CD patients, and those with dysbiosis exhibited a limited response to biological drugs. Pairwise differential abundance analyses revealed an increasing trend in the abundance of an unannotated genus from the Clostridiales order, Gemmiger genus and an unannotated genus from the Rikenellaceae family, which were consistently identified in greater abundance in HC. The Clostridium genus was more abundant in CD patients. At baseline, a greater abundance of the Odoribacter and Ruminococcus genera was found in IBD patients who responded to biologics at 14 weeks, whereas a genus identified as SMB53 was more enriched at 52 weeks. The Collinsella genus showed a higher prevalence among non-responder IBD patients. Additionally, a greater abundance of an unclassified genus from the Barnesiellaceae family and one from Lachnospiraceae was observed in IBD patients responding to Vedolizumab at 14 weeks. Our analyses showed global microbial diversity, mainly in CD. This indicated the absence or depletion of key taxa responsible for producing short-chain fatty acids (SCFAs). We also identified an abundance of pathobiont microbes in IBD patients at baseline, particularly in non-responders to biologic therapies. Furthermore, specific bacteria-producing SCFAs were abundant in patients responding to biologics and in those responding to Vedolizumab. [ABSTRACT FROM AUTHOR]

BackgroundApproximately 50% of patients who receive anti-CD19 CAR-T cells relapse, and new immunotherapeutic targets are urgently needed. We recently described CD72 as a promising target in B-cell malignancies and developed nanobody-based CAR-T cells (nanoCARs) against it. This cellular therapy design is understudied compared with scFv-based CAR-T cells, but has recently become of significant interest given the first regulatory approval of a nanoCAR in multiple myeloma.MethodsWe humanized our previous nanobody framework regions, derived from llama, to generate a series of humanized anti-CD72 nanobodies. These nanobody binders were inserted into second-generation CD72 CAR-T cells and were evaluated against preclinical models of B cell acute lymphoblastic leukemia and B cell non-Hodgkin's lymphoma in vitro and in vivo. Humanized CD72 nanoCARs were compared with parental ("NbD4") CD72 nanoCARs and the clinically approved CD19-directed CAR-T construct tisangenlecleucel. RNA-sequencing, flow cytometry, and cytokine secretion profiling were used to determine differences between the different CAR constructs. We then used affinity maturation on the parental NbD4 construct to generate high affinity binders against CD72 to test if higher affinity to CD72 improved antitumor potency.ResultsToward clinical translation, here we humanize our previous nanobody framework regions, derived from llama, and surprisingly discover a clone ("H24") with enhanced potency against B-cell tumors, including patient-derived samples after CD19 CAR-T relapse. Potentially underpinning improved potency, H24 has moderately higher binding affinity to CD72 compared with a fully llama framework. However, further affinity maturation (KD

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Investigate a composite score to evaluate the relationship between alignment proportionality and risk of distal junctional kyphosis (DJK). METHODS: 84 patients with minimum 1 year follow-up were included (age = 61.1 ± 10.3 years, 64.3% women). The Cervical Score was constructed using offsets from age-adjusted normative values for sagittal vertical axis (SVA), T1 Slope (TS), and TS minus cervical lordosis (CL). Individual points were assigned based on offset with age-adjusted alignment targets and summed to generate the Cervical Score. Rates of mechanical failure (DJK revision or severe DJK [DJK> 20° and ΔDJK> 10°]) were assessed overall and based on Cervical Score. Logistical regressions assessed associations between early radiographic alignment and 1-year failure rate. RESULTS: Mechanical failure rate was 21.4% (N = 18), 10.7% requiring revision. By multivariate logistical regression: 3-month T1S (OR: .935), TS-CL (OR:0.882), and SVA (OR:1.015) were independent predictors of 1-year failure (all P < .05). Cervical Score ranged (-6 to 6), 37.8% of patients between -1 and 1, and 50.0% with 2 or higher. DJK patients had significantly higher Cervical Score (4.1 ± 1.3 vs .6 ± 2.2, P < .001). Patients with a score ≥3 were significantly more likely to develop a failure (71.4%) with OR of 38.55 (95%CI [7.73; 192.26]) and Nagelkerke r2 .524 (P < .001). CONCLUSION: This study developed a composite alignment score predictive of mechanical failures in CD surgery. A score ≥3 at 3 months following surgery was associated with a marked increase in failure rate. The Cervical Score can be used to analyze sagittal alignment and help define realignment objectives to reduce mechanical failure.

Abstract Cadmium (Cd) pollution is a serious threat to food safety and human health. Minimizing Cd uptake and enhancing Cd tolerance in plants are vital to improve crop yield and reduce hazardous effects to humans. In this study, we designed three Cd concentration stress treatments (Cd1: 0.20 mg·kg−1, Cd2: 0.60 mg·kg−1, and Cd3: 1.60 mg·kg−1) and two foliar silicon (Si) treatments (CK: no spraying of any material, and Si: foliar Si spraying) to conduct pot experiments on soil Cd stress. The results showed that spraying Si on the leaves reduced the Cd content in brown rice by 4.79–42.14%. Si application increased net photosynthetic rate (Pn) by 1.77–4.08%, stomatal conductance (Gs) by 5.27–23.43%, transpiration rate (Tr) by 2.99–20.50% and intercellular carbon dioxide (CO2) concentration (Ci) by 6.55–8.84%. Foliar spraying of Si significantly increased the activities of superoxide dismutase (SOD) and peroxidase (POD) in rice leaves by 9.84–14.09% and 4.69–53.09%, respectively, and reduced the content of malondialdehyde (MDA) by 7.83–48.72%. In summary, foliar Si spraying protects the photosynthesis and antioxidant system of rice canopy leaves, and is an effective method to reduce the Cd content in brown rice.

Abstract Background Evidence has shown that the individual metrics in Life’s Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn’s disease (CD). We also tested whether genetic susceptibility could modify these associations. Methods A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0–49), moderate CVH (50–79), and high CVH (80–100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status. Results Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20–0.45; CD: 0.33, 95% CI: 0.20–0.57) was observed in participants with both high CVH and low genetic risk. Conclusions Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD.

CD28 and CTLA4 are T cell coreceptors that competitively engage B7 ligands CD80 and CD86 to control adaptive immune responses. While the role of CTLA4 in restraining CD28 costimulatory signaling is well-established, the mechanism has remained unclear. Here, we report that human T cells acquire antigen-presenting-cell (APC)-derived B7 ligands and major histocompatibility complex (MHC) via trogocytosis through CD28:B7 binding. Acquired MHC and B7 enabled T cells to autostimulate, and this process was limited cell-intrinsically by CTLA4, which depletes B7 ligands trogocytosed or endogenously expressed by T cells through cis-endocytosis. Extending this model to the previously proposed extrinsic function of CTLA4 in human regulatory T cells (Treg), we show that blockade of either CD28 or CTLA4 attenuates Treg-mediated depletion of APC B7, indicating that trogocytosis and CTLA4-mediated cis-endocytosis work together to deplete B7 from APCs. Our study establishes CTLA4 as a cell-intrinsic molecular sink that limits B7 availability on the surface of T cells, with implications for CTLA4-targeted therapy.

• NMR is the gold standard for determining the solution structures of G-quadruplexes. • Higher-order G-quadruplexes (xG4s) are often not amenable to characterization by NMR. • We show how NMR can be utilized in an integrative structural biology (ISB) approach to study xG4s. • We illustrate the ISB method and provide resources and best practices for those new to the field. Guanine-rich nucleic acids can form intramolecularly folded four-stranded structures known as G-quadruplexes (G4s). Traditionally, G4 research has focused on short, highly modified DNA or RNA sequences that form well-defined homogeneous compact structures. However, the existence of longer sequences with multiple G4 repeats, from proto-oncogene promoters to telomeres, suggests the potential for more complex higher-order structures with multiple G4 units that might offer selective drug-targeting sites for therapeutic development. These larger structures present significant challenges for structural characterization by traditional high-resolution methods like multi-dimensional NMR and X-ray crystallography due to their molecular complexity. To address this current challenge, we have developed an integrated structural biology (ISB) platform, combining experimental and computational methods to determine self-consistent molecular models of higher-order G4s (xG4s). Here we outline our ISB method using two recent examples from our lab, an extended c-Myc promoter and long human telomere G4 repeats, that highlights the utility and generality of our approach to characterizing biologically relevant xG4s. [ABSTRACT FROM AUTHOR]

[Objective] Black rock series contain high amounts of cadmium (Cd) and selenium (Se). During weathering and soil formation on the rocks, the chemical form transformation and release of Cd and Se from the rocks can have an impact on the surrounding ecological environment. [Methods] In this study, a black rock series distribution area of Hetang formation of the Lower Cambrian was selected in northwest Zhejiang. By collecting horizonal soil samples from soil profiles along different parts of the terrain (hill upslope, hill middle slope, hill downslope, inter hill valley bottom and valley terrace), the quantity and chemical form transformation patterns of Cd and Se during the process of weathering soil formation and weathering material migration of the black rock series were discussed. [Results] The results showed that total Cd and total Se in the soil decreased from parent rock to soil. The loss of Cd and Se in the weathered matter of black rock series increased with the increasing of transportation distance along the hilly slope, and the loss of Cd and Se in the process of evolution from slope deposit to diluvium was greater than that from residual to slope deposit. The Cd and Se lost from the weathered materials could affect the contents of Cd and Se in the topsoil derived from the alluvial of the downstream river in the way of water diffusion, but the degree of influence decreased with the increasing of distance. With the increasing of the transportation distance of weathered materials and the evolution of soil, the transformation of carbonate bound Cd and residual Cd to water-soluble Cd, exchangeable Cd, organic matter bound Cd and oxide bound Cd occurred. The residual Se gradually activated and transformed into exchangeable Se, organic matter bound Se and oxide bound Se. The results also showed that soil water-soluble Cd, exchangeable Cd (Se) and organic matter bound Cd (Se) showed an increasing trend toward the surface. The organic enrichment and topsoil enrichment of Se were more obvious than those of Cd. [Conclusion] The results indicated that the weathering of black rock series could not only directly affect the contents of soil Cd and Se in their distribution area through residue, but also affect the contents of soil Cd and Se in the surrounding areas through water diffusion.

Abstract Soil microorganisms play pivotal roles in driving essential biogeochemical processes in terrestrial ecosystems, and they are sensitive to heavy metal pollution. However, our understanding of multiple environmental factors interaction in heavy metal polluted paddy fields to shape microbial community assembly remain limited. In the current study, we used 16S rRNA amplicon sequencing to characterize the microbial community composition in paddy soils collected from a typical industry town in Taihu region, eastern China. The results revealed that Cd and Pb were the major pollutant, and Proteobacteria, Acidobacteria and Chloroflexi were the dominate indigenous bacterial phyla. Linear regression and random forest analysis demonstrated that soil pH was the most important predictor of bacterial diversity. Mantel analysis showed that bacterial community structure was mainly driven by pH, CEC, silt, sand, AK, total Cd and DTPA-Cd. The constructed bacterial co-occurrence network, utilizing a random matrix theory-based approach, exhibited non-random with scale-free and modularity features. The major modules within the networks also showed significant correlations with soil pH. Overall, our study indicated that soil physiochemical properties made predominant contribution to bacterial community diversity, structure and their association in Cd/Pb polluted paddy fields. These findings expand our knowledge of the key environmental drivers and co-occurrence patterns of bacterial community in polluted paddy fields.

Abstract Fe–Mn oxide modified biochar (FMBC) was produced to explore its potential for remediation of Hg–Cd contaminated paddy soils. The results showed that the application of FMBC decreased the contents of bioavailable Hg and Cd by 41.49–81.85% and 19.47–33.02% in contrast to CK, while the amount of labile organic carbon (C) fractions and C-pool management index (CPMI) was increased under BC and FMBC treated soils, indicating the enhancement of soil C storage and nutrient cycling function. Dry weight of different parts of Oryza sativa L. was enhanced after the addition of BC and FMBC, and the contents of Fe and Mn in root iron–manganese plaques (IMP) were 1.46–2.06 and 6.72–19.35 times higher than those of the control groups. Hg and Cd contents in brown rice under the FMBC treatments were significantly reduced by 18.32–71.16% and 59.52–72.11% compared with the control. FMBC addition altered the composition and metabolism function of soil bacterial communities, especially increasing the abundance of keystone phyla, including Firmicutes, Proteobacteria and Actinobacteria. Partial least squares path modelling (PLSPM) revealed that the contents of Na2S2O3–Hg, DTPA–Cd and IMP were the key indicators affecting Hg and Cd accumulation in rice grains. These results demonstrate the simultaneous value of FMBC in remediation of Hg and Cd combined pollution and restoring soil fertility and biological productivity. Graphical Abstract

Wild boars, being a common game species, inhabit regions across Eurasia, the southern regions of Asia and certain Indonesian islands. Being omnivorous and due to their relatively long lifespan, wide distribution and a relatively high number of shot animals per annual legal hunting season, they are suitable to be biological indicators of occurrence of heavy metals. Concentrations of cadmium, lead, arsenic and mercury were analyzed by atomic absorption spectrometry and cold vapor atomic absorption spectrometry in the livers of free-living wild boars (n = 58) from two locations in the Republic of North Macedonia. In all four examined heavy metals, no statistically significant difference between the locations was found (p > 0.05). The mean levels of heavy metals were Cd 0.391 mg/kg and 0.339 mg/kg; Pb 0.213 mg/kg and 0.204 mg/kg; Hg 0.034 mg/kg and 0.037 mg/kg; As 0.035 mg/kg and 0.029 mg/kg in the livers of boars from Bitola and Gevgelija hunting sites, respectively. Although some samples (two samples of Hg, ten samples of Cd and two samples of Pb) exceeded the legal limits, the average values for all heavy metals were far below the maximum permitted values. These findings are promising since they suggest that the ecosystem in the Republic of North Macedonia is stable concerning heavy metal pollution.

Recent surveys have demonstrated the widespread presence of ultraviolet (UV) emission in early-type galaxies (ETGs), suggesting the existence of star formation in many of these systems. However, potential UV contributions from old and young stars, together with model uncertainties, makes it challenging to confirm the presence of young stars using integrated photometry alone. This is particularly true in ETGs that are fainter in the UV and have red UV-optical colours. An unambiguous way of disentangling the source of the UV is to look for structure in UV images. Optical images of ETGs, which are dominated by old stars, are smooth and devoid of structure. If the UV is also produced by these old stars, then the UV images will share this smoothness, while, if driven by young stars, they will exhibit significant structure. We compare the UV and optical morphologies of 32 ETGs (93 per cent of which are at z < 0.03) using quantitative parameters (concentration, asymmetry, clumpiness, and the Sérsic index), calculated via deep UV and optical images with similar resolution. Regardless of stellar mass, UV-optical colour or the presence of interactions, the asymmetry and clumpiness of ETGs is significantly larger (often by several orders of magnitudes) in the UV than in the optical, while the UV Sérsic indices are typically lower than their optical counterparts. The ubiquitous presence of structure demonstrates that the UV flux across our entire ETG sample is dominated by young stars and indicates that star formation exists in all ETGs in the nearby Universe. [ABSTRACT FROM AUTHOR]

The INSPIRE project has built the largest sample of ultra-compact massive galaxies (UCMGs) at 0.1 < z < 0.4 and obtained their star formation histories (SFHs). Due to their preserved very old stellar populations, relics are the perfect systems to constrain the earliest epochs of mass assembly in the Universe and the formation of massive early-type galaxies. The goal of this work is to investigate whether a correlation exists between the degree of relicness (DoR), quantifying the fraction of stellar mass formed at z > 2, and the other stellar population parameters. We use the Full-Index-Fitting method to fit the INSPIRE spectra to single stellar population (SSP) models. This allows us to measure, for the first time, the slope of the IMF, as well as stellar metallicity [M/H], [Mg/Fe], [Ti/Fe], and [Na/Fe] ratios, and study correlations between them and the DoR. Similarly to normal-sized galaxies, UCMGs with larger stellar masses have overall higher metallicities. We found a correlation between the IMF slope and the DoR, that, however, breaks down for systems with a more extended SFH. An even stronger dependency is found between the IMF and the fraction of mass formed at high- z. At equal velocity dispersion and metallicity, galaxies with a higher DoR have a larger dwarf-to-giant ratio, i.e. a bottom heavy IMF, than that of low-DoR counterparts. This might indicate that the cosmic epoch and therefore different formation scenarios influence the fragmentation of the star formation cloud and hence might be the explanation for IMF variations detected in massive ETGs. [ABSTRACT FROM AUTHOR]

Soil microorganisms play pivotal roles in driving essential biogeochemical processes in terrestrial ecosystems, and they are sensitive to heavy metal pollution. However, our understanding of multiple environmental factors interaction in heavy metal polluted paddy fields to shape microbial community assembly remain limited. In the current study, we used 16S rRNA amplicon sequencing to characterize the microbial community composition in paddy soils collected from a typical industry town in Taihu region, eastern China. The results revealed that Cd and Pb were the major pollutant, and Proteobacteria, Acidobacteria and Chloroflexi were the dominate indigenous bacterial phyla. Linear regression and random forest analysis demonstrated that soil pH was the most important predictor of bacterial diversity. Mantel analysis showed that bacterial community structure was mainly driven by pH, CEC, silt, sand, AK, total Cd and DTPA-Cd. The constructed bacterial co-occurrence network, utilizing a random matrix theory-based approach, exhibited non-random with scale-free and modularity features. The major modules within the networks also showed significant correlations with soil pH. Overall, our study indicated that soil physiochemical properties made predominant contribution to bacterial community diversity, structure and their association in Cd/Pb polluted paddy fields. These findings expand our knowledge of the key environmental drivers and co-occurrence patterns of bacterial community in polluted paddy fields. [ABSTRACT FROM AUTHOR]

This study aims to quantitatively evaluate the effectiveness of modified biochar in reducing soil Cd availability and Cd content in plants by performing a metaanalysis using data from 58 papers. Modified biochar enhances the surface function and adsorption efficiency of biochar, making it a cost-effective modifier for immobilizing heavy metals. Various factors influence the cadmium (Cd) passivation effect of modified biochar, including the materials used, modification methods, and specific modified materials, warranting further research and clarification. On average, the application of modified biochar results in a significant reduction in soil Cd availability by 65.01% and Cd content in plants by 70.72%. Notably, biochar made from lignocellulose as a raw material exhibits an impressive reduction effect of 96.34% on soil Cd availability. Furthermore, organic modified biochar and acid-base modified biochar demonstrate reduction effects of 119.53% and 112.03%, respectively, for soil Cd availability. When considering plant uptake, modified biochar composed of herbs and combined modified biochar show better Cd reduction effects, with respective reductions of 100.53% and 88.87%. The optimal application rate of modified biochar falls within the range of 2%–3%, leading to a reduction of effective Cd in soil by 76.94% and Cd content in plants by 88.88%. This meta-analysis underscores the potential of modified biochar in remediating Cd-contaminated soil, offering valuable insights for the preparation and application of this material. [ABSTRACT FROM AUTHOR]