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Carbohydrates are fundamental molecules involved in nearly all aspects of lives, such as being involved in formating the genetic and energy materials, supporting the structure of organisms, constituting invasion and host defense systems, and forming antibiotics secondary metabolites. The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases. During 2000 to 2021, totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents. Here we provide a comprehensive review on the chemical structures, activities, and clinical trial results of these carbohydrate-based drugs, which are categorized by their indications into antiviral drugs, antibacterial/antiparasitic drugs, anticancer drugs, antidiabetics drugs, cardiovascular drugs, nervous system drugs, and other agents. A systemic review of the total 54 carbohydrate-based drugs, which approved during 2000–2021, is comprehensively summarized according to their chemical structures, activities, and clinical trial results. [Display omitted] [ABSTRACT FROM AUTHOR]

Cancer stem-like cells (CSLCs) and anoikis resistance play crucial roles in the metastasis of cancers. However, it remains unclear whether CSLCs are related to anoikis resistance in intrahepatic cholangiocarcinoma (ICC). Here we identified a group of stemness-related anoikis genes (SRAGs) via bioinformatic analysis of public data. Accordingly, a novel anoikis-related classification was established and it divided ICC into C1 and C2 type. Different type ICC displayed distinct prognosis, molecular as well immune characteristics. Furthermore, we found one key SRAGs via several machine learning algorithms. HK2 was up-regulated in tumor-repopulating cells (TRCs) of ICC, a kind of CSLCs with a potent resistance to anoikis. Its up-regulation may be caused by the activation of MTORC1 signaling in ICC-TRCs. And inhibition of HK2 significantly increased anoikis and decreased migration as well invasion in ICC-TRCs. Our studies provide an insight into the molecular mechanism underlying the resistance of ICC-TRCs to anoikis and enhance the evidences for targeting HK2 in ICC. [Display omitted] • We identified several stemness-related anoikis genes in intrahepatic cholangiocarcinoma. • We constructed a novel anoikis-related classification for intrahepatic cholangiocarcinoma. • We found that cancer stem-like cells displayed anoikis resistance due to its up-regulated MTORC1/HK2 axis. • Inhibiting HK2 effectively inhibited migration and invasion of cancer stem-like cells via promoting anoikis. [ABSTRACT FROM AUTHOR]

Carboxymethyl chitosan (CMCS)-based complex coacervate has attracted much attention in drug oral delivery due to its pH-responsive property. As a unique ampholyte polymer, the self-coacervation of CMCS has great research potential. In this work, CMCS self-coacervates were prepared by adjusting the pH of the CMCS aqueous solution close to its isoelectric point. The Fourier-transformed infrared spectroscopy (FTIR) results revealed that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were involved in the self-coacervation of CMCS. The obtained self-coacervates presented a dense surface structure, and were stable at a wide pH range of 3.0–6.0, and gradually dissolved under basic conditions. Although self-coacervation decreased the crystallinity and thermal stability of CMCS, the obtained coacervates showed excellent pH-responsive properties and ionic strength stability. We also investigated its potential in lactoferrin (LF) encapsulation and oral delivery. The CMCS self-coacervates exhibited a high encapsulation efficiency (EE) of 94.79 ± 0.49% and loading capacity (LC) of 26.29 ± 0.52% when the addition amount of LF was 2 mg. The simulated gastric digestion results demonstrated that CMCS self-coacervates could protect more than 80% of LF from hydrolysis and maintain the bioactivities of LF. Accordingly, the self-coacervation of CMCS could be used as a pH-responsive encapsulation and delivery strategy. [ABSTRACT FROM AUTHOR]

The present study aimed to improve the sustainable availability of insoluble polypeptide aggregates that are inevitably produced during protein hydrolysis. A controlled pH-response method was employed to process goat milk casein insoluble polypeptide aggregates and obtain soluble nano-delivery carriers (GMC). Zein-GMC-chitosan (Z-GMC-CS) ternary nanoparticles (NPs) were successfully designed by spontaneous assembly with enhanced solubility, stability, and bioaccessibility of lutein (Lut). Results showed that a novel ternary nanoscale stabilized hydrophilic particle (Lut-Z-GMC-CS) was successfully designed with a particle size of 122.8 ± 3.2 nm. Morphological results demonstrated the smooth spherical shape of the new ternary NPs. Successful encapsulation of Lut by these NPs was verified by FT-IR and XRD analysis. Incorporating GMC in Lut-Z-CS (Lut-Z-GMC-CS) NPs significantly improved their water solubility, stability, antioxidant activity, and bioaccessibility. The gastrointestinal digestion stability of Lut-Z-GMC-CS NPs could control the effective release of Lut into the intestine. Moreover, the ussing-chamber experiment indicated penetration of the ternary composite NPs into the intestinal wall to get absorbed by the body. These findings would facilitate the development of sustainable peptide by-products for novel high-quality delivery platforms. [Display omitted] • Soluble peptide aggregates (GMC) were prepared by pH-response method. • Zein-GMC-chitosan ternary nanoparticles were fabricated to deliver Lutein. • GMC combined with CS enhanced the various stability and bioaccessibility of Lutein. • GMC and Lutein exerted a synergistic effect in the ternary nanoparticles. [ABSTRACT FROM AUTHOR]

Cell-based therapy is a promising strategy to alleviate neuropathic pain caused by spinal cord injury (SCI). We transplanted olfactory ensheathing cells (OECs) into SCI rats with neuropathic pain and quantitatively detected the sensory nerve function. The expression levels of P2X4 receptor (P2X4R), 200 kD neurofilament heavy polypeptide (NF200), and glial fiber acidic protein (GFAP) were measured by immunofluorescence and Western blot analyses. Results showed that NF200 expression significantly increased, GFAP expression decreased, and sensory nerve function improved. In addition, OEC transplantation inhibited the overexpression of P2X4R, which plays an important role in neuropathic pain. Thus, OEC is a candidate target for the treatment of sensory functional loss and P2X4R-mediated neuropathic pain caused by SCI. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. Based on our previous discovery of two non-ATP competitive FGFR1 inhibitors, A114 and A117, we designed and screened a series of compounds with the framework of bisaryl-1,4-dien-3-one. Among them, D12 and D15 exhibited the most potent FGFR1 inhibitory activity, which was ATP-independent. Furthermore, a quantitative structure-activity relationship analysis of 41 analogs demonstrated that the specific structural substitutions alter their bioactivities. Molecular docking and dynamics simulation analysis indicated the hydrophobic interaction at the FGFR1- D12/D15 interaction was dominant. Evaluation for anti-gastric cancer efficacy of D12 and D15 indicated effective inhibition of cell proliferation, apoptosis induction and cell cycle arrest. Thus, these two FGFR1 inhibitors have therapeutic potential in the treatment of gastric cancer, and this study provides will contribute to the rational design of novel non-ATP competitive FGFR1 inhibitors. [ABSTRACT FROM AUTHOR]

(−)-Epicatechin gallate (ECG), as a natural α-amylase inhibitor, has received extensive attention. However, poor liposolubility of ECG limits its application. In this study, lipophilic derivatives of ECG (1A-ECG, 2A-ECG, 1B-ECG, and 2B-ECG) were synthesized by Lipozyme TLIM (Thennomyces lanuginosus) and their mechanism on delaying starch digestion was investigated. The results showed that the conversion of ECG exceeded 70% under optimal conditions. Interestingly, compared with ECG, the inhibitory activities of ECG derivatives on α-amylase decreased, while the inhibitory activity of 1A-ECG on α-amylase increased. Though the main force between ECG and 1A-ECG with α-amylase was induced by hydrogen bond, hydrophobic interaction was the main force between other derivatives with α-amylase. However, the addition of four ECG derivatives can effectively reduce the proportion of rapidly digestible starch, and delay the digestion of starch. This study may expand the applications of ECG and provide a theoretical basis for 1A-ECG to delay the digestion of starch. [Display omitted] • (−)-Epicatechin gallate (ECG) derivatives were synthesized. • 1A-ECG possessed superior inhibitory actions on α-amylase than ECG. • The main interactive force of 1A-ECG on α-amylase was hydrogen bond. • Larger molecular size of ECG derivatives prevents their combination with α-amylase. • Four ECG derivatives would convert more RDS to RS than ECG. [ABSTRACT FROM AUTHOR]

A total of 77 jujube, longan and chaste honey samples were collected from 18 different areas of China. Thirteen types of phenolic acids in the honey samples were analysed using high-performance liquid chromatography with electrochemical detection (HPLC–ECD). Moreover, HPLC–ECD fingerprints of the monofloral honey samples were established. From the analysis of the HPLC–ECD fingerprints, common chromatography peak information was obtained, and principal component analysis and discriminant analysis were performed using selected common chromatography peak areas as variables. By comparing with phenolic acids as variables, using a chemometric analysis which is based on the use of common chromatography peaks as variables, 36 honey samples and 41 test samples could be correctly identified according to their floral origin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Goat milk whey protein peptides (GWP, <3 kDa) had stronger hypoglycemic activity. • GWP was encapsulated into niosomes using 4 phytosterols replace cholesterol. • Morphologically confirmed GWP was successfully loaded into liposomes and niosomes. • GWP niosomes have high simulated gastrointestinal and long-term storage stability. • GWP niosomes can significantly improve the bioaccessibility of GWP. This study sought to develop a nanoscale delivery system to enhance the stability and bioaccessibility of goat milk whey protein peptides. Goat milk whey protein was hydrolyzed by papain, and the hydrolysate was ultrafiltered to obtain a low molecular weight peptide (GWP, <3 kDa) with strong hypoglycemic activity. The GWP-loaded liposomes and niosomes encapsulation systems were prepared using phytosterols (ergosterol, β- sitosterol, mixed phytosterols, and stigmasterol) instead of cholesterol. Results showed that the GWP-loaded niosomes (GWP-NS) prepared from β- sitosterol had the higher GWP encapsulation efficiency (90.46 ± 4.02 %) and the smaller particle size (92.07 ± 9.8 nm) than liposomes (GWP-LS). Additionally, the morphological results showed that two GWP-loaded systems were smooth and spherical, and the FT-IR spectroscopy confirmed the successful formation of the peptide-loaded system. Compared with GWP, GWP-LS and GWP-NS showed the higher stability under different pH, temperature, and NaCl concentration conditions, especially GWP-NS. Furthermore, GWP-NS could significantly improve the retention rate of GWP during simulated gastrointestinal digestion, in vitro bioaccessibility, and hypoglycemic activity. These findings suggest that β- sitosterol could be a potential membrane stabilizer alternative to cholesterol, and GWP niosomes could be a potential new drug delivery system. [ABSTRACT FROM AUTHOR]

Lower Cretaceous volcaniclastic sandstones, widely distributed in the Tethyan Himalaya, provide insights into evolution of the Tethyan Himalaya and the continental breakup of Eastern Gondwana. Here we present the petrological, geochronological and geochemical data from the Lower Cretaceous volcaniclastic sandstones at the Babazhadong section, eastern Tethyan Himalaya. The geochronological data show that the youngest detrital zircons in the lowest volcaniclastic sandstones have U–Pb age of (134 ± 4 Ma), therefore were deposited post late Valanginian. The volcaniclastics are predominantly comprised by mafic detritus in the lower part, while felsic grains become more abundant up-section. The proportion of volcaniclastics in the sandstones also increases upwards. Geochemical data of mafic detritus indicate within-plate basalt affinity. Based on these observations, in combination with the stratigraphic correlation of coeval volcaniclastic sandstones deposited along the length of the Himalayas, we conclude that the volcaniclastics in the Babazhadong area are within-plate affinity, probably related to the opening of deep, crust cross-cutting fractures along the northern margin of Greater India. [ABSTRACT FROM AUTHOR]

Abstract: Background and objectives: Intrahepatic biliary cystadenoma and biliary cystadenocarcinoma are extremely rare neoplasms of the liver. They share similar radiological characteristics, and the clinicopathological features are poorly defined. We aim to provide an algorithm for preoperative differentiation of the two diseases. Methods: Patients who underwent liver resection between May 2001 and May 2011 at Peking Union Medical College Hospital with biliary cystadenoma (20 cases) and biliary cystadenocarcinoma (10 cases) were reviewed. Results: Significant differences were shown in age (P =0.030), gender (P =0.002) and symptom duration (P =0.012). Most biliary cystadenomas occurred in women ≤60 years old (85%), whilst most biliary cystadenocarcinomas occurred in older males (50%). Shorter symptom duration indicated a higher risk of biliary cystadenocarcinoma. Arterial blood flow and wall/nodule enhancement tended to be more common in biliary cystadenocarcinoma, but the difference was not significant (P =0.348). A score system was developed. The case-by-case validation and leave-one-out cross-validation showed an accuracy of 95.5% and 90.9%, respectively. The discriminative accuracy for cases from another hospital during the same period was 90.9%. Conclusions: Older age, male gender, and shorter symptom duration are associated with higher possibility of biliary cystadenocarcinoma. Location and blood supply by radiology might be instrumental but still need further verification. [Copyright &y& Elsevier]

The Indo-Pacific Warm Pool (IPWP) is the largest source of atmospheric heating and moisture on Earth, energizing the global moisture and energy budgets and controlling global ocean-atmosphere circulation. However, the mechanisms driving orbital-scale changes in hydroclimate and proxy records of precipitation isotopic composition remain poorly known. Here, we use the isotope-enabled Transient Climate Evolution (iTRACE) experiment to investigate long-term hydroclimate and precipitation isotope changes in the IPWP during the last deglaciation, and their response to different climate forcings (sea level and ice sheet, greenhouse gases, orbital forcing, and meltwater flux). The simulations suggest land-sea configuration as the main factor driving long-term hydroclimate and precipitation isotope changes. The exposure of NW Australian shelf (before 14 ka) excited Bjerknes feedbacks across the equatorial Indian Ocean (IO), leading to a warm/wet western IO and cool/dry eastern IO dipole pattern, with overall drying and more enriched precipitation isotopic compositions over the Maritime Continent. However, the exposed Sunda Shelf and the main body of Sahul Shelf (before 12 ka) experienced locally dry conditions but more depleted precipitation isotopic compositions. Greenhouse gases and orbital forcing contribute to a weaker hydroclimate dipole pattern that opposes the effects of NW Australian shelf exposure. Different regions within the IPWP have different simulated sensitivities to these forcings. The heterogeneous responses of precipitation to different forcings across the Maritime Continent and location-dependent relationships between precipitation and its isotopic composition result from a variety of regional climatological processes and may explain the heterogeneity of isotopic records of hydroclimate around the IPWP. • Investigated deglacial hydroclimate and water isotope changes in IPWP using iTRACE. • Land-sea configuration drives deglacial trends of IPWP rainfall and its isotopes. • Shelf exposure effect excites a zonal hydroclimate dipole pattern along tropical IO. • GHGs and orbital forcing lead to a weaker and opposite dipole pattern across the IO. [ABSTRACT FROM AUTHOR]

From the latest Cretaceous (late Campanian to Maastrichtian, ~76-66 Ma) through the earliest Paleogene, changes of greenhouse climate were linked to catastrophic geological events and massive biotic extinction and were primarily derived from marine records. Here we present a high-resolution, tightly age-constrained, clay mineralogical record from the Sifangtai and Mingshui formations of the terrestrial Songliao Basin, northeast China. Smectite and illite are the dominant clay species and are derived from the weathering of parent rocks and/or pedogenesis in paleosols. We use the percentage ratio of smectite and illite, the illite chemistry index, and the percentage ratio of phyllosilicate clay minerals and quartz in clay fractions for paleoclimatic reconstruction. Our results show that from the latest Cretaceous through the earliest Paleogene, values of all three clay mineralogical proxies in the Songliao Basin are generally higher during warming intervals than those during cooling intervals. This dataset suggests that warming caused strengthened moisture delivery from the Pacific, increasing precipitation and intensified chemical weathering, whereas cooling was accompanied by increasing dryness and physical weathering. Across the Cretaceous-Paleogene boundary, the warming likely related to Deccan volcanism, the transient cooling afterwards, and the warming in the earliest Paleogene are characterized by changes in the illite chemistry index and paleosol carbonate stable isotopic excursions as shown in previously published records, reflecting fluctuations in hydroclimate and weathering intensity. Our work demonstrates that terrestrial climate and weathering intensity in the mid-latitude Songliao Basin fluctuated during the latest Cretaceous through the earliest Paleogene and sensitively responded to global climate changes. [ABSTRACT FROM AUTHOR]

• An annual precipitation record was reconstructed via Santa Barbara Basin sediments. • Southern California precipitation variance is teleconnected to ENSO. • Southern California interannual precipitation variance increased after 4.4 ka. • ENSO variance was influenced by the changing ITCZ and Aleutian Low positions. The variability of El Niño-Southern Oscillation (ENSO) on centennial to millennial time-scales is poorly understood due to the insufficient length, continuity, or resolution of existing paleoclimate records. Here we present a new, continuous, sub-annually resolved scanning XRF Ti record from marine sediments collected from Santa Barbara Basin (SBB) to reveal interannual precipitation changes in Southern California for the past 9000 yrs. Interannual precipitation variability in Southern California is closely related to ENSO through an atmospheric teleconnection with the tropical Pacific. Thus, Southern California precipitation reconstructions provide an opportunity to explore ENSO variability through time. Wavelet analysis of the SBB Ti record demonstrates interannual (2–7 yrs) precipitation variance was relatively weak prior to 4.4 ka, and significantly increased after 4.4 ka. Our record demonstrates a relationship between Southern California precipitation and the tropical Pacific and extratropical climate. The inferred increase of ENSO variability during the late Holocene is generally consistent with the published tropical Pacific ENSO records, and could be associated with a southward shift of the Intertropical Convergence Zone (ITCZ). Meanwhile, a deeper, westward-shifted Aleutian Low after 4.4 ka may have strengthened the ENSO teleconnection between the tropical Pacific and Southern California, contributing to the amplified interannual precipitation variance in the SBB record. Community Earth System Model (CESM) simulations through the Holocene (0, 3, 6, 9 ka) support the role of both the ITCZ and the AL in the enhancement of interannual precipitation variability in Southern California. [ABSTRACT FROM AUTHOR]

In the work, a novel filamentou sodium alginate (SA) /ε-polylysine (PL) fiber with excellent mechanical properties and controllable sizes is prepared in an efficient and environmentally friendly manner via continuous pulling of an electrostatically assembled SA/PL composites at the contact interface of aqueous solutions of cationic polyelectrolyte ε-PL and anionic natural polysaccharide SA. The SA/PL fiber exhibits good antibacterial activity, low cytotoxicity, anti-hemolysis, bioadhesion, and environmental friendliness due to its natural raw materials and green preparation process. In vivo experiments have shown that the SA/PL fiber can promote the healing and repair of skin wounds on the backs of mice via resistance to pathogen infection, reduction of inflammation, and anti-allogeneic allergy of the wound. In summary, these results demonstrate that the SA/PL fiber is a green and biosafe multifunctional natural polymer material, with potential applications in suturing wound. [Display omitted] • A size controllable SA/PL fiber is prepared efficiently via electrostatic self-assembly. • SA/PL fiber has excellent biocompatibility, antibacterial and bioadhesion fuctions. • SA/PL fiber can promote wound healing as an antiallergic surgical suture in vivo. [ABSTRACT FROM AUTHOR]

Traffic flow prediction is pivotal in providing reliable information for intelligent traffic systems. Unexpected events, such as bad weather, unavoidably impact the precision of traffic flow prediction. Therefore, to achieve accurate traffic flow prediction results in road networks under bad weather, a novel Traffic-Weather Generative Adversarial Network (TWeather-GAN model) is developed. This model comprises a Generator and a Discriminator. The Generator incorporates both the traffic and weather modules to extract the spatiotemporal patterns hidden in traffic flow and weather data. In the traffic and weather modules, the gated convolutional layer, Encoder-Decoder architecture, and attention mechanism are established. In the Discriminator, the gated convolutional layer and bidirectional long short-term memory neural network are introduced. Traffic flow data under fog, strong wind, and heavy rain are selected to test the seven baseline models and the proposed model, and the ablation experiments are conducted to analyze the mechanism of the proposed model. The experiments demonstrate that the TWeather-GAN model outperforms the baseline models under bad weather, and makes the prediction error have an average reduction of 0.20%–34.81%, 3.21%–35.22%, and 9.46%–39.10%, respectively, under one-step prediction, three-step prediction, and six-step prediction. Furthermore, establishing the gated convolutional layer and the weather module enhances the accuracy of traffic flow prediction under bad weather. Results show that traffic flow fluctuations and distributions differ under fog and strong wind, and heavy rain affects the trend of traffic flow over one day. [ABSTRACT FROM AUTHOR]

Drying across much of the Indo-Pacific Warm Pool (IPWP) during the Last Glacial Maximum (LGM) has been widely recognized from interpretations of sedimentological, geochemical, and paleoecological records. Reconstructions of precipitation isotopic compositions have emerged as a powerful tool to reconstruct rainfall amount in many tropical regions, yet it has proven difficult to reconcile precipitation isotope records from the IPWP with records of widespread drying. To evaluate the signals preserved in precipitation isotope records, we produced new hydrogen and carbon isotope records from Lake Towuti and Lake Matano in Sulawesi, Indonesia using long-chain n -alkanes. We then compared these new records to existing n-alkanoic acid records from the same lakes and compiled available marine runoff, salinity, leaf wax hydrogen isotope (δ2H wax), and leaf wax carbon isotope (δ13C wax) records in the IPWP. During the last deglaciation, marine runoff and salinity proxies reveal that precipitation amount began to increase dramatically between ∼12.3 ka at the end of the Younger Dryas. A principal component analysis of precipitation isotope records indicates a shift from more 2H-enriched to 2H-depleted waxes at ∼12.3 ka as sea level rise inundates most of the Sunda and Sahul shelves, coincident with runoff and salinity proxies, suggesting precipitation isotopes respond strongly to rainfall amount in this region. Over 70% of IPWP δ13C wax records show a transition from more to less 13C-enriched waxes beginning about 19.9 ka, prior to the reconstructed increases in precipitation. We suggest that vegetation shifted in response to the changing seasonality of precipitation. The dramatic changes in the IPWP during the last deglaciation highlight the capacity for the region to experience dynamic changes in precipitation, vegetation, and atmospheric circulation. • IPWP runoff and salinity indicate increasing precipitation starting at ∼12.3 ka • IPWP precipitation isotope records show a shift to more depletion at ∼12.3 ka • IPWP δ13C wax records show a shift at ∼19.9 ka, prior to increased precipitation • Changing seasonality of precipitation may have caused the early shift in vegetation [ABSTRACT FROM AUTHOR]

In this work, a novel synthesis strategy of sodium alginate/carboxymethyl chitosan hydrogel beads promoted by hydrogen bond was described. The beads were prepared by dropping the blends of two polymers into the citric acid solution. Besides hydrogen bonding, electrostatic interactions were also involved in the formation of the hydrogel beads. The thermal stability experiments revealed that the more the content of carboxymethyl chitosan, the better the thermal stability of the beads. The beads exhibited excellent pH sensitivity, pH reversibility, and lactoferrin loading capacity. The swelling ratio of the bead and its protein releasing profile was pH-dependent, which could prevent premature protein release in the gastric environment. Also, the circular dichroism results demonstrated that lactoferrin could maintain its structure during the loading and releasing process. The obtained results revealed that the hydrogel beads prepared in this work could be used as a potential protein carrier for oral delivery. [Display omitted] • A novel and green method was proposed to synthesize SA/CMCS hydrogel beads. • Hydrogen bonding promoted the formation of the hydrogel beads. • The beads showed excellent pH sensitivity and protein encapsulation capacity. • The beads could prevent premature protein release in a harsh gastric environment. [ABSTRACT FROM AUTHOR]

A new type of double-network hydrogel, cross-linked with microcrystalline cellulose grafted with ε-polylysine (MCC-PL) and N , N -methylene bisacrylamide/acrylic acid, was synthesised to efficiently inhibit bacterial proliferation and remove heavy metals. The physicochemical properties of the MCC-PL hydrogel (MCC-PLH) were characterised using scanning electronic microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and differential thermogravimetric analysis. The adsorption results showed that the optimal adsorption conditions were temperature of 313 K at pH of 5 and 6 of Pb2+ and Cu2+, respectively. The adsorption mechanism of MCC-PLH5 was successfully determined using Freundlich isotherm, pseudo-second kinetics, and intra-particle diffusion model, in conjunction with X-ray photoelectron spectroscopy. Adsorption thermodynamic studies indicated that the process was spontaneous and endothermic. Antibacterial experiments showed that PL-grafted MCC hydrogel exhibited more efficient and durable antibacterial activity than MCC, indicating its potential for water decontamination. Unlabelled Image • Microcrystalline cellulose grafted with ε-polylysine is synthesised successfully. • Double-network composite hydrogel is prepared to remove Pb2+/Cu2+ from aqueous solutions. • MCC-PLH exhibited well antimicrobial efficiency against both the E. coli and S. aureus bacteria. • MCC-PLH has a potential for water decontamination. [ABSTRACT FROM AUTHOR]

• Tumor volume is prognostic for locoregionally advanced nasopharyngeal carcinoma. • Epstein-Barr virus DNA loads during chemoradiotherapy is also a prognostic indicator. • A risk stratification system was developed incorporating these two factors. • The system improved survival prediction and clinical decision-making. To investigate the value of integrating primary gross tumor volume (GTV p) and gross tumor volume of nodes (GTV n) after induction chemotherapy (IC) and dynamic changes in plasma cell-free Epstein-Barr virus DNA (cfEBV DNA) during sequential chemoradiotherapy (CRT) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We retrospectively reviewed 988 patients with LA-NPC undergoing IC plus concurrent chemoradiotherapy (CCRT) between 2014 and 2018. The entire cohort was divided into four subgroups according to tumor volume and the cfEBV DNA load. Using a supervised statistical clustering approach, we stratified the subgroups into three clusters. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were calculated using Kaplan-Meier analysis and inter-group differences were compared using the log-rank test. We observed that GTV p & GTV n and cfEBV DNA postIC & cfEBV DNA postCRT were powerful prognostic factors for OS (p = 0.004, p < 0.001, p < 0.001, and p < 0.001, respectively). The survival curves of the three clusters were significantly different. The 5-year OS for the low-risk, intermediate-risk and high–risk clusters were 97.0%, 86.2% and 77.1% (all P values < 0.001), respectively. The risk stratification system showed better predictive performance than the current tumor-node-metastasis (TNM) classification for OS (area under curve [AUC]: 0.653 versus 0.560, p < 0.001), DFS (AUC: 0.639 versus 0.540, p < 0.001), DMFS (AUC: 0.628 versus 0.535, p < 0.001) and LRRFS (AUC: 0.616 versus 0.513, p < 0.001). Both tumor volume and the cfEBV DNA level during sequential CRT are effective prognostic indicators for patients with high-risk LA-NPC. The developed risk stratification system incorporating above factors improved survival prediction and demonstrated potential value in decision-making. [ABSTRACT FROM AUTHOR]

EF24 is an IKKβ inhibitor (IC 50 : 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC 50 : 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKKβ-NF-κB signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKKβ inhibitor as anti-tumor precursor. [ABSTRACT FROM AUTHOR]

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) preserved in lake sediments are increasingly used to investigate past terrestrial temperatures. brGDGTs are ubiquitous in sedimentary environments, well-preserved, and the number of methyl groups in different brGDGTs is generally controlled by temperature. Current brGDGT calibrations largely rely on empirical correlations between the relative abundances of different brGDGTs in surface sediments and either mean annual or warm season air temperatures. These approaches may introduce complications in global temperature calibrations due to differences in the seasonality of temperature and variations in brGDGT production with latitude that are difficult to constrain. Here, we report new brGDGTs data from lake surface sediments obtained throughout the tropics including South America (n = 57), East Africa (n = 21), and Southeast Asia (n = 13), and revisit globally distributed brGDGT data. We find a uniform response of brGDGTs to mean annual air temperature across the tropics despite differences in the environmental and geological conditions in different regions highlighting the dominant influence of temperature on brGDGT distributions. brGDGTs in mid- and high latitude sediment show a qualitatively similar but quantitatively different response to those in the tropics. We show that temperature seasonality can partially explain the latitudinal differences, implying the need for latitudinally-dependent brGDGT calibrations and/or improved observations and models to constrain seasonal effects on brGDGTs. Combining our new data with previously published brGDGT data, we develop and apply improved temperature calibrations. • brGDGT distributions were measured in 91 tropical lakes' surface sediments. • Tropical brGDGTs show uniform response to mean annual air temperature. • We observe a different response of brGDGTs to temperature in high latitude lakes. • Seasonality causes different brGDGT responses in the tropics and mid-to high latitudes. • We provide improved regional and global lacustrine brGDGT temperature calibrations. [ABSTRACT FROM AUTHOR]

• PAH records in Liaodong Bay provides the first detailed reconstruction of industrial activities;. • PAH variations can be divided into four episodes linked to industrialization process since 1815. • Dominant PAH sources of Northeast China shift from wood to coal and petroleum over time;. • PAH fluxes could be used to track the trend for regional anthropogenic CO 2 emissions. Polycyclic aromatic hydrocarbons (PAHs) are excellent tracers for fossil fuel combustion, natural fires and petroleum contamination, and have been widely used for reconstructing past wildfires and industrial activities at a variety of time scales. Here, for the first time, we obtain a high resolution (annual to decadal scale) record of PAHs from two parallel marine sediment cores from the Liaodong Bay, Northeastern China to reconstruct the industrial activities, spanning the past ∼ 200 years from 1815 to 2014. Our data indicate that PAH variations can be divided into four episodes: I) low (probably near background) PAHs from natural fires and domestic wood combustion during the pre-industrial period from 1815 to 1890; II) slightly increased (but with large fluctuations) PAH concentrations derived from intermittent warfare during the World War (1891–1945) and increased industrial activities after 1946 (1946–1965); III) a period of stagnation and, in some cases, reduction in PAHs during the "Cultural Revolution" (1966 to 1979); and IV) a rapid and persistent rise in PAHs post 1979 linked to fast economic development, with PAH concentrations doubled from 1979 to 2014. Changes in PAH distributions demonstrate major shifts in the dominant types of fuels over time from vegetation/wood, to coal and wood, followed by coal and petroleum (including vehicle emissions) over the past 200 years. We find that PAH records also show similar trend to domestic economy and the estimated regional Anthropocene CO 2 emissions from industrial activities, suggesting sedimentary PAH fluxes could be used as an indirect and qualitative proxy to track the trend for regional anthropogenic CO 2 emissions. [Display omitted] [ABSTRACT FROM AUTHOR]

Tannic acid (TA) can strongly interact with proteins to improve the stability of protein-based nanoparticles. In the present study, the complexation of TA with bovine lactoferrin (LF) was investigated at pH 6.0. The size and turbidity of the LF-TA complexes did not change significantly until the LF/TA molar ratio was over a critical value of 1:8. Zeta potential of LF-TA was gradually negative as the TA content increased, indicating that there were electrostatic interactions between LF and TA. The circular dichroism (CD) spectroscopy confirmed that TA could further reduce the α-helix and increase the β-sheet content of LF significantly, resulting in a more compact structure of LF. The fluorescence spectra revealed that the interaction between LF and TA caused intramolecular quenching of LF, and the values of K sv increased with temperature, indicating that static quenching was involved in the interaction between LF and TA. Thermodynamic parameters indicated that the reaction between LF and TA proceed spontaneously, and hydrophobic interactions were the major interaction force. Molecular docking suggested that the binding site of TA and LF was in the inter-leaf region where the two lobes were connected by a spiral. Besides, the proteolytic digestion experiments testified that the addition of TA could reduce the digestibility of LF. Information derived from this work suggests that the addition of TA in LF systems could improve the digestive stability of bio-complex for oral delivery of functional constituents. [Display omitted] • Interaction between bovine lactoferrin (LF) and tannic acid (TA) was analyzed. • The interaction between LF and TA led to a more compact structure of LF. • Hydrophobic interaction was predominant in LF-TA complex. • The interaction between LF and TA reduced the digestibility of LF. [ABSTRACT FROM AUTHOR]