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The high cell density, immobilization and stability of biofilms are ideal characteristics for bacteria in resisting antibiotic therapy. CsgD is a transcription activating factor that regulates the synthesis of curly fimbriae and cellulose in Escherichia coli, thereby enhancing bacterial adhesion and promoting biofilm formation. To investigate the role of CsgD in biofilm formation and stress resistance in bacteria, the csgD deletion mutant ΔcsgD was successfully constructed from the engineered strain E. coli BL21(DE3) using the CRISPR/Cas9 gene-editing system. The results demonstrated that the biofilm of ΔcsgD decreased by 70.07% (p < 0.05). Additionally, the mobility and adhesion of ΔcsgD were inhibited due to the decrease in curly fimbriae and extracellular polymeric substances. Furthermore, ΔcsgD exhibited a significantly decreased resistance to acid, alkali and osmotic stress conditions (p < 0.05). RNA-Seq results revealed 491 differentially expressed genes between the parent strain and ΔcsgD, with enrichment primarily observed in metabolism-related processes as well as cell membrane structure and catalytic activity categories. Moreover, CsgD influenced the expression of biofilm and stress response genes pgaA, motB, fimA, fimC, iraP, ompA, osmC, sufE and elaB, indicating that the CsgD participated in the resistance of E. coli by regulating the expression of biofilm and stress response. In brief, the transcription factor CsgD plays a key role in the stress resistance of E. coli, and is a potential target for treating and controlling biofilm. [ABSTRACT FROM AUTHOR]

Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. However, it is unclear how boron affects biofilm formation in E. coli, particularly recombinant E. coli with intracellular enzymes. This study screened different boron derivatives to explore their effect on biofilm formation. The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. Results showed that boron derivatives promote AI-2 activity in QS system. After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. Moreover, treatment with H3BO3 (0.6 mM) increased biomass by 88.54%. Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0–0.6 mM H3BO3 and NaBO2 (R2 > 0.8). Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) contrast agents, in contrast to the plethora of fluorescent agents available to target disease biomarkers or exogenous implants, have remained predominantly non-specific. That is, they do not preferentially accumulate in specific locations in vivo because doing so necessitates longer contrast retention, which is contraindicated for current gadolinium (Gd) agents. This double-edge sword implies that Gd agents can offer either rapid elimination (but lack specificity) or targeted accumulation (but with toxicity risks). For this reason, MRI contrast agent innovation has been severely constrained. Gd-free alternatives based on manganese (Mn) chelates have been largely ineffective, as they are inherently unstable. In this study, we present a Mn(III) porphyrin (MnP) platform for bioconjugation, offering the highest stability and chemical versatility compared to any other T1 contrast agent. We exploit the inherent metal stability conferred by porphyrins and the absence of pendant bases (found in Gd or Mn chelates) that limit versatile functionalization. As proof-of-principle, we demonstrate labeling of human serum albumin, a model protein, and collagen hydrogels for applications in in-vivo targeted imaging and material tracking, respectively. In-vitro and in-vivo results confirm unprecedented metal stability, ease of functionalization, and high T1 relaxivity. This new platform opens the door to ex-vivo validation by fluorescent imaging and multipurpose molecular imaging in vivo. [ABSTRACT FROM AUTHOR]

The frictional drag in turbulent flow can be drastically reduced by the addition of minute amounts of suitable linear flexible high-molecular-weight polymers, and the various physical characteristics of the polymers used are known to be closely related to the drag reduction efficiency. This feature article briefly reviews polymer additives and factors in the system affecting turbulent drag reduction in external flow, more specifically in a rotating disk flow. [ABSTRACT FROM AUTHOR]

Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day–night cycle. This internal timekeeping mechanism is built on autoregulatory transcription–translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin–proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination. In this review, we summarize the roles that known E3 ubiquitin ligases play in the circadian clocks of two popular model organisms: mice and fruit flies. We also discuss emerging evidence that implicates the N-degron pathway, an alternative proteolytic system, in the regulation of circadian rhythms. We conclude the review with our perspectives on the potential for the proteolytic and non-proteolytic functions of E3 ubiquitin ligases within the circadian clock system. [ABSTRACT FROM AUTHOR]

The profound impact of the Khmer Empire on Southeast Asia renders the Angkor Period particularly significant in guiding contemporary societies to advocate and promote policies that respond to climate change. We present a new continuous multi-proxy speleothem dataset from Tonle Sap Lake Basin, investigating hydroclimate variability and the paleoenvironment of Cambodia during the Angkor Period from the 9th to 15th centuries. In addition, two important climatic events on a decadal scale are clearly reconstructed. The first is the reduction of precipitation between 800 and 1000 AD and the relatively significant drought that the regional environment may have experienced from 950 to 1000 AD. The second is the anomalous wet period between 1000 and 1200 AD, during which the Southern Oscillation Index also reached its negative peak after a thousand years. The wet and dry conditions are highly consistent with the El Niño-dominated and northward Intertropical Convergence Zone. [ABSTRACT FROM AUTHOR]

The Indo-Pacific, a vast biogeographic of Earth, is influenced by both the Indian and East Asian monsoons. Despite its geographical importance, this region has been less studied compared to East Asia and India. Here, we present speleothem records from southern Thailand that cover the last 1500 years, including a hiatus during the Little Ice Age, providing insights into the interactions among climate dynamics, human influences, and ecological responses to climate change. Notably, our records lack the characteristic cold and warm periods observed in other regions, such as the Dark Ages Cold Period and Medieval Warm Period, which may reflect the complexity of the tropical climate system or the region's unique topography. The analysis reveals a link between ENSO multi-decadal variability and hydroclimate conditions in southern Thailand, as evidenced by speleothem δ18O. Furthermore, a comparison between speleothem δ13C and the Normalized Difference Vegetation Index (NDVI) indicates significant vegetation changes in the last three decades, corresponding with increased atmospheric CO2 levels and expansion of agricultural land due to human activities during the Current Warm Period. Additionally, our study suggests that an abrupt increase in sea surface temperatures may enhance vegetation growth in the Indo-Pacific by influencing atmospheric circulation and increasing precipitation. [ABSTRACT FROM AUTHOR]

Speleothem δ13C in monsoonal China differs from speleothem δ18O, which is widely used as a climatic proxy for several complex control reasons. Nevertheless, δ13C records have the potential to reveal the implications of hydroclimatic changes. This study reports a speleothem δ13C record from Didonghe (DDH) Cave in central China spanning 34 to 13 kyr BP. After we investigated the factors that influence speleothem δ13C, we found that the δ13C record showed that DDH Cave can prompt directional shifts via local hydroclimatic changes, such as in vegetation types, biomass, and rock–water interaction processes, suggesting that δ13C is mainly controlled by the local hydroclimate. Ensemble empirical mode decomposition (EEMD) results revealed a coupling relationship between δ18O and δ13C on multiple timescales, which suggested that changes in precipitation caused by large-scale monsoonal circulation are controlled by regional hydrological conditions to a great extent. However, the hydrological conditions of the cave were relatively mild and humid during the last glacial maximum (LGM), which revealed the impact of evaporation on changes in the region's hydrological conditions. We also found that the δ18O and δ13C profiles decoupled when δ13C changed with a shift in the location of the westerly during HS1. The δ13C record correlates well with other paleoclimate records, suggesting that regional hydrological conditions are also modulated by the Earth's internal and external driving factors. [ABSTRACT FROM AUTHOR]

As prominent abrupt climatic events during the last deglaciation and the early Holocene, the Younger Dryas (YD) and the 8.2 ka events have been intensely discussed to reveal the relationship between their phases and intensities, and their underlying mechanisms based on massive marine and terrestrial archives. However, the related paleoclimate records with sufficient resolution and/or precise age constraints from the Southern Hemisphere, especially East Africa, are relatively sparse, hindering our comprehensive understanding about the phases of these two events. Here, we provide a precisely dated record of an aragonite-calcite stalagmite covering 11.3–13.5 ka BP from northwest Madagascar to unravel the arid conditions during the YD, in contrast to the pluvial conditions in the 8.2 ka event that has been evidenced before. Changes in austral summer precipitation related to the Intertropical Convergence Zone (ITCZ) have always been interpreted to be the primary means of controlling regional rainfall amounts and thus the δ18O variations in stalagmite. However, ITCZ's meridional migration alone is not enough to interpret the opposite hydroclimatic conditions during the YD and the 8.2 ka events in northwest Madagascar. The variation in convection intensity within the ITCZ combined with the rainfall dipole mode in East Africa, and the redistribution of the duration of the ITCZ's presence at different latitudes might be responsible for this phenomenon. In addition, sea surface temperature could play a nonnegligible role. [ABSTRACT FROM AUTHOR]

The Asian monsoon (AM) has direct and profound effects on the livelihoods of residents in South Asia and East Asia. Modern observations have shown multi-decadal alternations of flood and drought periods in these regions, likely influenced by climatic processes such as the Atlantic Multidecadal Oscillation and the Pacific Decadal Oscillation. However, our understanding of the multi-decadal variability of the AM under different climatic conditions remains uncertain. In this study, we collected an annually laminated and 780-mm stalagmite (sample number: BJ7) from Binjia (BJ) Cave in southwestern China, which is deeply influenced by the Asian monsoon system. Based on this sample, we established 6-year resolution and multi-proxy records for the Asian summer monsoon (ASM) variabilities during the early last termination, spanning from 18.2 to 16.1 ka BP. Measurements of five pairs of uranium and thorium solutions for 230Th dating were conducted using a multi-collector inductively coupled plasma mass spectrometer (MC-ICP- MS), and 374 pairs of stable isotope (δ18O and δ13C) analyses were run on a Kiel Carbonate Device connected with Finnigan MAT-253 at Nanjing Normal University. The chronology for this sample was established by annual layer counting anchored with 230Th dating results. Our BJ7 δ18O record replicates well with other Chinese δ18O records on the general trend, all of which are superimposed by frequent multidecadal-scale fluctuations at approximately 60 years periodicity. Inspection of the 60-year band in BJ7 δ18O and δ13C records and results of the cross-wavelet analysis indicate coherent changes in the ASM and biomass production/karst processes during most of the studied period. In addition, the 60-year band of BJ7 and NGRIP δ18O records are consistent, implying the impacts of the high-latitude North Atlantic or Atlantic Multidecadal Oscillation on the ASM. Our study suggests that the 60-year variability should be an intrinsic feature of the climate system regardless of glacial or interglacial backgrounds. [ABSTRACT FROM AUTHOR]

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids. [ABSTRACT FROM AUTHOR]

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 μM to 9.2 μM. [ABSTRACT FROM AUTHOR]

In recent years, a chaotic system is considered as an important pseudo-random source to pseudo-random number generators (PRNGs). This paper proposes a PRNG based on a modified logistic chaotic system. This chaotic system with fixed system parameters is convergent and its chaotic behavior is analyzed and proved. In order to improve the complexity and randomness of modified PRNGs, the chaotic system parameter denoted by floating point numbers generated by the chaotic system is confused and rearranged to increase its key space and reduce the possibility of an exhaustive attack. It is hard to speculate on the pseudo-random number by chaotic behavior because there is no statistical characteristics and infer the pseudo-random number generated by chaotic behavior. The system parameters of the next chaotic system are related to the chaotic values generated by the previous ones, which makes the PRNG generate enough results. By confusing and rearranging the output sequence, the system parameters of the previous time cannot be gotten from the next time which ensures the security. The analysis shows that the pseudo-random sequence generated by this method has perfect randomness, cryptographic properties and can pass the statistical tests. [ABSTRACT FROM AUTHOR]

The search for a continuous continental record of interglacial periods in semi-arid regions is problematic due to the absence of stable and continuous sedimentary systems over time in this type of climate. In this work, a relatively stable basin is described and analyzed during the last interglacial period in a semi-arid region of the western Mediterranean. For this purpose, a geomorphological, stratigraphic and sedimentological study has been carried out, with dating through 230Th. A semi-endorheic Pleistocene section has been identified, with two units that correspond to a fluvial-lacustrine system (unit P1) and an alluvial system (unit P2). Unit P1 has been dated to the MIS 5e interglacial episode. A framework for future studies is described, in which the Aljezares Pleistocene basin can be considered as a possible source of paleoenvironmental and paleoclimatic information in semi-arid regions from the last interglacial period. [ABSTRACT FROM AUTHOR]

We previously reported on the comparison of proteomic data between seven tissue types of a novel "iron prawn" species. However, no transcripts or metabolic information are available for this species. We therefore performed shotgun LC–MS/MS metabonomic and RNA-seq analyses of the total protein from "iron prawns". KEGG analysis revealed that the largest group consisted of a total of 114 KEGG pathway proteins, comparing the "iron prawns" with the normal prawns. A total of 423 peptides, corresponding to metabolic pathways, ABC transporters, starch and sucrose metabolism, insulin resistance/secretion, fatty digestion and absorption, and lipid metabolism, were identified. The pathways of carbohydrate and amino acid metabolism decreased in female iron prawns, while organic acid and its derivatives increased. However, the pathway of organic acid and its derivatives decreased and lipid metabolism increased in the male iron prawns. The pathways of choline metabolism in cancer and glycerophospholipid/histidine/propanoate metabolism have been significantly affected in iron prawns. Our work provides insight into the understanding of the formation mechanism of the "iron prawn". [ABSTRACT FROM AUTHOR]

Four new cyclohexylideneacetonitrile derivatives 1–4, named menisdaurins B–E, as well as three known cyclohexylideneacetonitrile derivatives—menisdaurin (5), coclauril (6), and menisdaurilide (7)—were isolated from the hypocotyl of a mangrove (Bruguiera gymnorrhiza). The structures of the isolates were elucidated on the basis of extensive spectroscopic analysis. Compounds 1–7 showed anti-Hepatitis B virus (HBV) activities, with EC50 values ranging from 5.1 ± 0.2 μg/mL to 87.7 ± 5.8 μg/mL. [ABSTRACT FROM AUTHOR]

Mood disorders negatively impact the lives of hundreds of millions of individuals worldwide every year, yet the precise molecular mechanisms by which they manifest remain elusive. Circadian dysregulation is one avenue by which mood disorders are thought to arise. SOX2 is a transcription factor that is highly expressed in the murine suprachiasmatic nucleus (SCN), the circadian master clock, and has been recently found to be an important regulator of Per2, a core component of the molecular clock. Genetic ablation of the Sox2 gene in GABAergic neurons selectively impacts SCN neurons, as they are one of very few, if not the only, GABAergic populations that express Sox2. Here, we show that GABAergic-restricted ablation of Sox2 results in anxio-depressive-like phenotypes in mice as observed in the elevated plus maze, forced swim test, tail suspension test, and sucrose preference test. We further observe a reduction in basal and/or forced swim-induced c-Fos expression, a marker of neuronal activation, in the nucleus incertus, arcuate nucleus, and dentate gyrus of Sox2 conditional knockout (cKO) mice. Given the restricted disruption of SOX2 expression in the SCN of Sox2 cKO mice, we propose that their mood-associated phenotypes are the consequence of a dysregulated central clock that is unable to communicate appropriately timed signals to other brain nuclei that regulate affective behaviors. [ABSTRACT FROM AUTHOR]

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 (Sox2), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6, in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN. [ABSTRACT FROM AUTHOR]

Simple Summary: Drug development and therapeutic approaches for treating cancer have shifted towards incorporating more multimodality approaches that harness the immune system. Despite innovative and notable advances in immunotherapy, challenges associated with variations in patient response rates and efficacies on select tumors minimize the overall effectiveness of these immunotherapy approaches. This review provides an overview of the current immunotherapy options available, followed by epigenetic immunomodulators that may enhance and transmogrify immunotherapy effectiveness. These approaches are positioned to harness trained immunity, improve immune response rates, and increase the efficacy of immunotherapies. Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer presents a unique clinical problem because of the variety of cellular subtypes present, including cancer stem cells (CSCs). Breast CSCs can induce the formation of new blood vessels at the site of tumor growth and a develop metastatic phenotype by enhancing a stromal cell response, similar to that of the primary breast cancer. The aim of this study was to investigate breast cancer cells cultured in stromal stem cell factor-supplemented media to generate 3D spheroids that exhibit increased stem-like properties. These 3D stem-like spheroids reproducibly and efficiently established orthotopic breast cancer xenografts in the athymic nude rat. This approach enables a means to develop orthotopic tumors with a stem-like phenotype in a larger athymic rat rodent model of human breast cancer. Therapeutic targeting of stem cells needs to be strategically developed to control tumor growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes present, including cancer stem cells (CSCs). The development of 3D stem-like properties of human breast tumor spheroids in stem cell factor conditioned media was investigated in orthotopic xenografts for enhanced tumorgenicity in the athymic nude rat model. MCF-7, ZR-75-1, and MDA-MB-231 breast cancer cell lines were cultured in serum-free, stem cell factor-supplemented medium under non-adherent conditions and passaged to generate 3rd generation spheroids. The spheroids were co-cultured with fetal lung fibroblast (FLF) cells before orthotopic heterotransplantation into the mammary fat pads of athymic nude rats. Excised xenografts were assessed histologically by H&E staining and immunohistochemistry for breast cancer marker (ERB1), proliferation marker (Ki67), mitotic marker (pHH3), hypoxia marker (HIF-2α), CSC markers (CD47, CD44, CD24, and CD133), and vascularization markers (CD31, CD34). Breast cancer cells cultured in stem cell factor supplemented medium generated 3D spheroids exhibited increased stem-like characteristics. The 3D stem-like spheroids co-cultured with FLF as supporting stroma reproducibly and efficiently established orthotopic breast cancer xenografts in the athymic nude rat. [ABSTRACT FROM AUTHOR]

Biodiesel offers an important alternative to fossil fuel. In this work, Eversa Transform 2.0 lipase was immobilized onto 3-aminopropyltriethoxysilane (APTES) modified silica clay (SC) by glutaraldehyde. The characteristics of the functionalized supports and the immobilized lipase were investigated by FTIR, TEM, BET, and XRD. The results show that the optimal conditions of lipase immobilization are as follows: 2% glutaraldehyde concentration, 15 mg/mL lipase concentration and incubating at 25 °C for 60 min. The immobilized lipase showed a high tolerance to temperature and pH variation in comparison to the free lipase. The immobilized lipase on SC was applied as a biocatalyst for the synthesis of biodiesel from methanol and canola oil. A biodiesel yield of 86% was obtained at a temperature of 45 °C via a three-step methanol addition. A conversion yield of 67% was maintained after reusing the immobilized lipase for five cycles. This work provides a strategy for the preparation of an efficient biocatalyst for the synthesis of biodiesel. [ABSTRACT FROM AUTHOR]

The central pacemakers of circadian timekeeping systems are highly robust yet adaptable, providing the temporal coordination of rhythms in behavior and physiological processes in accordance with the demands imposed by environmental cycles. These features of the central pacemaker are achieved by a multi-oscillator network in which individual cellular oscillators are tightly coupled to the environmental day-night cycle, and to one another via intercellular coupling. In this review, we will summarize the roles of various neurotransmitters and neuropeptides in the regulation of circadian entrainment and synchrony within the mammalian and Drosophila central pacemakers. We will also describe the diverse functions of protein kinases in the relay of input signals to the core oscillator or the direct regulation of the molecular clock machinery. [ABSTRACT FROM AUTHOR]