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The issue of bacterial resistance is an escalating problem due to the misuse of antibiotics worldwide. This study introduces a new antibacterial mechanism, the ferroptosis-like death (FLD) of bacteria, and an approach to creating green antibacterial nano-reactors. This innovative method leverages natural iron-containing ovotransferrin (OVT) assembled into an organic skeleton to encapsulate low-concentration adriamycin (ADM) for synthesizing eco-friendly nano-reactors. FLD utilizes the Fenton reaction of reactive oxygen species and ferrous ions to continuously produce ·OH, which can attack the bacterial cell membrane and destroy the cell structure to achieve bacteriostasis. The OVT@ADM nano-reactors are nearly spherical, with an average diameter of 247.23 nm and uniform particle sizing. Vitro simulations showed that Fe3+ in OVT@ADM was reduced to Fe2+ by glutathione in the bacterial periplasmic space, which made the structure of OVT loose, leading to a sustained slow release of ADM from OVT@ADM. The H2O2 continuously produced by ADM oxidized Fe2+ through the Fenton reaction to produce ·OH and Fe3+. The results of the antibacterial assay showed that OVT@ADM had a satisfactory antibacterial effect against S. aureus, and the inhibition rate was as high as 99.3%. The cytotoxicity results showed that the mitigation strategy significantly reduced the cytotoxicity caused by ADM. Based on the FLD mechanism, OVT@ADM nano-reactors were evaluated and applied to bacteriostasis. Therefore, the novel antibacterial mechanism and OVT@ADM by the green synthesis method have good application prospects. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the efficacy and safety of sertraline combined with low-dose aripiprazole in the treatment of obsessive-compulsive disorder in children and adolescents.MethodsA total of 62 cases pediatric patients aged 9~16 years who attended the outpatient clinic of a psychiatric hospital in Xiamen from June 2018 to May 2020 and met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for obsessive-compulsive disorder were enrolled in the study. The selected children were randomly classified into two groups for different treatments. Control group （n=30） received sertraline monotherapy， and study group （n=32） received sertraline combined with low-dose aripiprazole treatment. At the baseline and the end of the 2nd， 4th， 8th and 12th weeks of treatment， children were assessed using Children's Yale-Brown Obsessive Compulsive Scale （CY-BOCS） and Treatment Emergent Symptoms Scale （TESS）. Thereafter， the clinical efficacy and adverse reactions were compared between two groups.ResultsThe compulsive behavior dimensional score of CY-BOCS of study group was lower than that of control group at end of the 2nd and 4th weeks of treatment （t=-2.083， -2.176， P

As an essential nutrient, lutein (LUT) has the ability to aid in the prevention of eye diseases, cardiovascular diseases, and cancer. However, the application of LUT is largely restricted by its poor solubility and susceptibility to oxidative degradation. Thus, in this study, LUT-loaded nanogel (OVM-COS-LUT) was prepared by a self-assembly of ovomucin (OVM) and chitosan oligosaccharide (COS) to enhance the effective protection and bioavailability of LUT. The nanogel had excellent dispersion (PDI = 0.25) and an 89.96% LUT encapsulation rate. XRD crystal structure analysis confirmed that the encapsulated LUT maintained an amorphous morphology. In addition, the nanogel showed satisfactory stability with pH levels ranging from 2 to 9 and high ionic strengths (>100 mM). Even under long-term storage, the nanogel maintained an optimistic stabilization and protection capacity; its effective retention rates could reach 96.54%. In vitro, digestion simulation showed that the bioaccessibility and sustained release of OVM-COS-LUT nanogel was superior to that of free LUT. The nanogel provided significant antioxidant activity, and no significant harmful effects were detected in cytotoxicity analyses at higher concentrations. In summary, OVM-COS-LUT can be utilized as a potential safe oral and functional carrier for encapsulating LUT. [ABSTRACT FROM AUTHOR]

This study investigated the effect of alkalis on C3S hydration with and without incorporating aluminate phases. Pastes of 100% C3S and 90% C3S+10% metakaolin (MK) were prepared at 1%, 2%, and 3% Na2O content. X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were used to characterize the solid phase assemblages, and then the hydration degree of C3S. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to analyze the aqueous composition of pore solution. Mercury intrusion porosimetry (MIP) was used to measure the porosity of the hydrated pastes. The results highlighted the promoting effect of Na and the inhibiting effect of Al in pore solution on C3S hydration after a period of curing (90 days). Without incorporating metakaolin, the hydration degree of C3S continuously increased with the increase of Na concentration. Incorporating metakaolin into C3S can generate aluminate hydrates (carboaluminates, in this study), and the increased Na concentration can increase the dissolution or instability of carboaluminates and elevate the equilibrium Al concentration. Under this condition, the hydration degree of C3S fluctuated depending on the combined effect of Na and Al concentrations in pore solution on C3S hydration. [ABSTRACT FROM AUTHOR]

Morroniside is one of the most important iridoid glycosides from Cornus officinalis Sieb. et Zucc. In the present study, the pharmacokinetics and bioavailability studies of morroniside were conducted on Sprague-Dawley (SD) rats. A rat in situ intestinal perfusion model was used to characterize the absorption of morroniside. Caco-2 cells were used to examine the transport mechanisms of morroniside. The pharmacokinetic study of morroniside exhibited linear dose-proportional pharmacokinetic characteristics and low bioavailability (4.3 %) in SD rats. Its average Peff value for transport across the small intestinal segments changed from (3.09 ± 2.03) × 10−6 to (4.53 ± 0.94) × 10−6 cm s−1. In Caco-2 cells, the Papp values ranged from (1.61 ± 0.53) × 10−9 to (1.19 ± 0.22) × 10−7 cm s−1 for the apical to basolateral side and the Pratio values at three concentrations were all lower than 1.2. Morroniside showed poor absorption and it might not be a specific substrate of P-glycoprotein (P-gp).

Although many studies have attempted to reconstruct millennial‐scale hurricane patterns using various proxy‐based methods, it is still unclear what the most effective proxies are to identify storm surge deposits in different environmental settings. This study quantitatively compares the application of grain‐size, loss‐on‐ignition, stable isotopes, X‐ray fluorescence, and palynological proxies in paleotempestology from an organic‐rich environment in the Florida Everglades. The nonparametric tests indicate that only 9 among the 27 parameters (mean diameter, %water, %organic, %carbonate, Ca, Sr, Ca/Ti, Cl/Br, and marine microfossils) exhibited significant differences between storm‐surge and in situ deposits. The principal component analysis shows that five marine indicators (Sr, Ca, Ca/Ti, %Carbonate, and Marine microfossils) have the closest association with the allochthonous samples, while Cl/Br and Mz are the most sensitive proxies in low‐ and high‐energy environments, respectively. Moreover, organic geochemical proxies (e.g., δ13C and δ15N of bulk sedimentary organic matter) are ineffective for identifying storm‐surge deposits in organic‐rich mangrove environments. Plain Language Summary: To help objectively identify the occurrence of storm‐surge deposits in coastal sediment cores, this study uses a statistical approach to evaluate the effectiveness of 27 widely used sedimentological, organic and inorganic geochemical, and biological parameters in distinguishing allochthonous deposits from autochthonous deposits in an organic‐rich environment in the Florida Everglades. The results show that Ca, Sr, Ca/Ti, and marine microfossil are four of the most sensitive parameters to distinguish storm‐surge deposits in organic‐rich environments in south Florida. In addition, Cl/Br can be used to indicate storm surge inundation in further inland and lower‐energy environments. Moreover, organic geochemical proxies cannot effectively distinguish storm‐surge deposits from in situ deposits in mangrove‐dominated coastal zones. Future studies need to explore the use of more specific organic geochemical proxies (e.g., biomarker) in mangrove‐dominated environments and evaluate the effective proxies in detecting storm deposits from sandy, deltaic/estuarine, and nontropical coastal environments. Key Points: Ca, Sr, Ca/Ti, and marine microfossil are the most sensitive parameters to identify storm‐surge deposits in organic‐rich environmentsCl/Br can be used to indicate storm surge inundation in further inland and lower energy environmentsOrganic geochemical proxies cannot effectively distinguish storm‐surge deposits from in situ deposits in mangrove‐dominated coastal zones [ABSTRACT FROM AUTHOR]

The Asian interior has the largest mid-latitude arid zone in the Northern Hemisphere, and so has become increasingly attractive for studying the initiation and the past extent of aridification in this zone. Given the enormousness of the Asian interior, it remains unclear how old and extensive the eolian deposits might have been, and what wind regimes have been responsible for the formation of the mid-latitude arid zone. Here we report new eolian records of widespread Tertiary eolian deposits in a region far from the Chinese Loess Plateau, the giant Junggar inland basin of northwestern China. Our results demonstrate that the earliest eolian deposition initiated ca. 24 Ma. We interpret that the Tertiary eolian dust in the Junggar Basin was transported by westerly winds, possibly from areas in Kazakhstan; the dust differs from the airborne dust transported by winter monsoon winds from the deserts of Mongolia and northern China that accumulated on the Loess Plateau. These results further reveal that the climate pattern, similar to that of the present, has prevailed at least since the latest Oligocene in Central Asia. doi: 10.1130/G30776.1

The Tianshan Range is one of the longest and highest mountain belts in Central Asia, stretching east-west for ~2500 km. Uplift of this late Paleozoic orogenic belt resulted from intracontinentai deformation caused by the collision of the Indian and Eurasian plates during the Cenozoic era. To constrain the timing of Cenozoic tectonic deformation of the Tianshan Range, we analyzed the magnetostratigraphy of 3780-m-thick Neogene deposits from the Kuqa foreland basin of southern Tianshan. The geometry measurements and magnetic fabric data show that syntectonic growth strata began to accumulate at ~6.5 Ma ago, indicating that crustal shortening initiated in the latest Miocene. The increase in sedimentation rate and an abrupt change of the magnetic fabric parameters also occurred at 6.5 Ma, accompanied by onset of syntectonic growth strata. The latest Miocene crustal shortening is a significant tectonic event in the foreland basin of the southern Tianshan Range in response to the India-Eurasia collision. doi: 10.1130/G30278A.1

The Taklimakan Desert is the world's second-largest shifting sand desert, located in the rain shadow of the Tibetan Plateau. The initiation of desert formation in the Asian interior is one of the most prominent climate changes in the Northern Hemisphere during the Cenozoic Era. Dating the earliest formation of this desert is important for understanding the climatic effects of the uplifted Tibetan Plateau. Here we report 1071-m-thick Neogene deposits with intercalated eolian dune sands from the only outcrop in the central Taklimakan Desert. Based on paleomagnetic measurements, biostratigraphic age control, and previous electron spin resonance dating results, the oldest in situ eolian dune sands were confirmed to be ca. 7 Ma, much older than the previous reported wind-blown siltstone from the southern edge of the Taklimakan Desert. This new result indicates that desert conditions initiated ca. 7 Ma in the center of the Tarim Basin. We attribute this event to the late Cenozoic climatic deterioration and/or to the rain-shadow effect caused by late Miocene uplift of the northern Tibetan margin.

Abstract Background The receptors for adhesion of Plasmodium falciparum-infected red blood cells (RBC) in the placenta have been identified as chondroitin-4-sulphate (C4S) proteoglycans, and the more sulphate-rich chondroitin oligosaccharides have been reported to inhibit adhesion. Since the anti-malarial drug chloroquine accumulates in lysosomes and alters normal lysosomal processes, the effects of chloroquine on the lysosomal enzyme arylsulphatase B (ASB, N-acetylgalactosamine-4-sulphatase), which removes 4-sulphate groups from chondroitin-4-sulphate, were addressed. The underlying hypothesis derived from the recognized impairment of attachment of parasite-infected erythrocytes in the placenta, when chondroitin-4-sulphation was increased. If chloroquine reduced ASB activity, leading to increased chondroitin-4-sulphation, it was hypothesized that the anti-malarial mechanism of chloroquine might derive, at least in part, from suppression of ASB. Methods Experimental methods involved cell culture of human placental, bronchial epithelial, and cerebrovascular cells, and the in vitro exposure of the cells to chloroquine at increasing concentrations and durations. Measurements of arylsulphatase B enzymatic activity, total sulphated glycosaminoglycans (sGAG), and chondroitin-4-sulphate (C4S) were performed using in vitro assays, following exposure to chloroquine and in untreated cell preparations. Fluorescent immunostaining of ASB was performed to determine the effect of chloroquine on cellular ASB content and localization. Mass spectrometry and high performance liquid chromatography were performed to document and to quantify the changes in chondroitin disaccharides following chloroquine exposure. Results In the human placental, bronchial epithelial, and cerebrovascular cells, exposure to increasing concentrations of chloroquine was associated with reduced ASB activity and with increased concentrations of sGAG, largely attributable to increased C4S. The study data demonstrated: 1) decline in ASB activity following chloroquine exposure; 2) inverse correlation between ASB activity and C4S content; 3) increased content of chondroitin-4-sulphate disaccharides following chloroquine exposure; and 4) decline in extent of chloroquine-induced ASB reduction with lower baseline ASB activity. Confocal microscopy demonstrated the presence of ASB along the cell periphery, indicating extra-lysosomal localization. Conclusions The study data indicate that the therapeutic mechanism of chloroquine action may be attributable, at least in part, to reduction of ASB activity, leading to increased chondroitin-4-sulphation in human placental, bronchial epithelial, and cerebrovascular cells. In vivo, increased chondroitin-4-sulphation may reduce the attachment of P. falciparum-infected erythrocytes to human cells. Extra-lysosomal localization of ASB and reduced impact of chloroquine when baseline ASB activity is less suggest possible mechanisms of resistance to the effects of chloroquine.