Engineering Metallic Alloy Electrode for Robust and Active Water Electrocatalysis with Large Current Density Exceeding 2000 mA cm-2.

The amelioration of brilliantly effective electrocatalysts working at high current density for the oxygen evolution reaction (OER) is imperative for cost-efficient electrochemical hydrogen production. Yet, the kinetically sluggish and unstable catalysts remain elusive to large-scale hydrogen (H2) generation for industrial applications. Herein, a new strategy is demonstrated to significantly enhance the intrinsic activity of Ni1-xFex nanochain arrays through a trace proportion of heteroatom phosphorus doping that permits robust water splitting at an extremely large current density of 1000 and 2000 mA cm-2 for 760 h. The in situ formation of Ni2P and Ni5P4 on Ni1-xFex nanochain arrays surface and hierarchical geometry of the electrode significantly promote the reaction kinetics and OER activity. The OER electrode provides exceptionally low overpotentials of 222 and 327 mV at current densities of 10 and 2000 mA cm-2 in alkaline media, dramatically lower than benchmark IrO2 and is among the most active catalysts yet reported. Remarkably, the alkaline electrolyzer renders a low voltage of 1.75 V at a large current density of 1000 mA cm-2, indicating outperformed overall water splitting. The electrochemical fingerprints demonstrate vital progress toward large-scale H2 production for industrial water electrolysis.

Association of Lung Cancer Risk With the Presence of Both Lung Nodules and Emphysema in a Lung Cancer Screening Trial.

Background: The coexistence of emphysema and lung nodules could interact with each other and then lead to potential higher lung cancer risk. The study aimed to explore the association between emphysema combined with lung nodules and lung cancer risk. Methods: A total of 21,949 participants from the National Lung Screening Trial (NLST) who underwent low-dose computed tomography (LDCT) examination were included. Participants were categorized into four groups (NENN group (non-emphysema and non-nodules), E group (emphysema without nodules), N group (nodules without emphysema), and E + N group (nodules with emphysema)) according to whether there were lung nodules and emphysema. Multivariable Cox regression and stratified analyses were performed to estimate the association between the four groups and lung cancer risk. Results: Among the 21,949 participants, there were 9,040 (41.2%), 5,819 (26.5%), 4,737 (21.6%), and 2,353 (10.7%) participants in the NENN group, E group, N group, and E + N group. The risk of lung cancer incidence increased in turn in NENN group, E group, N group and E + N group. Compared with NENN group, the age-adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of lung cancer incidence were 2.07 (1.69 - 2.54) for E group, 4.13 (3.47 - 5.05) for N group, and 6.26 (5.14 - 7.62) for E + N group. The association was robust to adjustment for potential confounders (1.83 (1.47 - 2.27) for E group, 3.97 (3.24 - 4.86) for N group, and 5.23 (4.28 - 6.48) for E + N group). Comparable results as the lung cancer incidence were observed for lung cancer mortality, whether in age-adjusted model (E group: 1.85 (1.39 - 2.46), N group: 2.49 (1.89 - 3.29), E + N group: 4.27 (3.21 - 5.68)) or fully adjusted model (E group: 1.56 (1.15 - 2.11), N group: 2.43 (1.81 - 3.26), E + N group: 3.39 (2.50 - 4.61)). However, the trend of all-cause mortality risk among the four groups was somewhat different from that of lung cancer risk, whether in age-adjusted model (1.37 (1.21 - 1.54) for E group, 1.06 (0.92 - 1.21) for N group, and 1.75 (1.51 - 2.02) for E + N group) or fully adjusted model (1.26 (1.10 - 1.44) for E group, 1.09 (0.94 - 1.27) for N group, and 1.52 (1.30 - 1.79) for E + N group). Conclusion: Based on a large-scale lung cancer screening trial in the United States, this study demonstrated that either emphysema or lung nodules can increase lung cancer risk, and lung nodules combined with emphysema can further increase the lung cancer risk and all-cause mortality. The significance of these findings for lung cancer screening should be evaluated.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Unlocking the Potential of High Entropy Alloys in Electrochemical Water Splitting: A Review.

The global pursuit of sustainable energy is focused on producing hydrogen through electrocatalysis driven by renewable energy. Recently, High entropy alloys (HEAs) have taken the spotlight in electrolysis due to their intriguing cocktail effect, broad design space, customizable electronic structure, and entropy stabilization effect. The tunability and complexity of HEAs allow a diverse range of active sites, optimizing adsorption strength and activity for electrochemical water splitting. This review comprehensively covers contemporary advancements in synthesis technique, design framework, and physio-chemical evaluation approaches for HEA-based electrocatalysts. Additionally, it explores design principles and strategies aimed at optimizing the catalytic activity, stability, and effectiveness of HEAs in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. Through an in-depth investigation of these aspects, the complexity inherent in constituent element interactions, reaction processes, and active sites associated with HEAs is aimed to unravel. Eventually, an outlook regarding challenges and impending difficulties and an outline of the future direction of HEA in electrocatalysis is provided. The thorough knowledge offered in this review will assist in formulating and designing catalysts based on HEAs for the next generation of electrochemistry-related applications.

The terrestrial end-Permian mass extinction in the paleotropics postdates the marine extinction.

The end-Permian mass extinction was the most severe ecological event during the Phanerozoic and has long been presumed contemporaneous across terrestrial and marine realms with global environmental deterioration triggered by the Siberian Traps Large Igneous Province. We present high-precision zircon U-Pb geochronology by the chemical abrasion-isotope dilution-thermal ionization mass spectrometry technique on tuffs from terrestrial to transitional coastal settings in Southwest China, which reveals a protracted collapse of the Cathaysian rainforest beginning after the onset of the end-Permian marine extinction. Integrated with high-resolution geochronology from coeval successions, our results suggest that the terrestrial extinction occurred diachronously with latitude, beginning at high latitudes during the late Changhsingian and progressing to the tropics by the early Induan, spanning a duration of nearly 1 million years. This latitudinal age gradient may have been related to variations in surface warming with more degraded environmental conditions at higher latitudes contributing to higher extinction rates.

Oxidation of selected fluoroquinolones by ferrate(VI) in water: Kinetics, mechanism, effects of constituents, and reaction pathways.

In this work, the oxidation of gatifloxacin (GAT), fleroxacin (FLE) and enoxacin (ENO) in aqueous solution by ferrate (Fe(VI)) was systemically investigated. Weak alkaline and high oxidant doses were favorable for the reaction. The pseudosecond-order rate constants were 0.18055, 0.29162, and 0.05476 L/(mg·min), and the activation energies were 25.13, 15.25, and 11.30 kJ/mol at pH = 8.00 and n(Fe(VI)):n(GAT) = 30:1, n(Fe(VI)):n(FLE) = 20:1, n(Fe(VI)):n(ENO) = 40:1 and a temperature of 25 °C. The maximum degradation rates of the GAT, FLE and ENO were 96.72%, 98.48% and 94.12%, respectively, well simulated by Response Surface Methodology. During the oxidation, the contribution of hydroxyl radicals (HO•) varied with time, whereas the final contribution was approximately 20% at 30 min. The removal efficiency was inhibited by anions by less than 10%, and cations by less than 25%, and significantly inhibited by high concentrations of humic acid. Moreover, two or three dominant reaction pathways were predicted, and the ring cleavages of quinolone and piperazine were mainly achieved through decarboxylation, demethlation and hydroxylation, and some pathways ended up with monocyclic chemicals, which were harmless to aquatic animals and plants. Theoretical calculations further proved that the reactions between FeO4- and neutral fluoroquinolone antibiotics were the major reactions. This work illustrates that Fe(VI) can efficiently remove fluoroquinolone antibiotics (FQs) in aqueous environments, and the results may contribute to the treatment of wastewater containing trace antibiotics and Fe(VI) chemistry.

Antigen-loaded flagellate bacteria for enhanced adaptive immune response by intradermal injection.

Since the skin limits the distribution of intradermal vaccines, a large number of dendritic cells in the skin cannot be fully utilized to elicit a more effective immune response. Here, we loaded the antigen to the surface of the flagellate bacteria that was modified by cationic polymer, thus creating antigen-loaded flagellate bacteria (denoted as 'FB-Ag') to overcome the skin barrier and perform the active delivery of antigen in the skin. The FB-Ag showed fast speed (∼0.2 µm s-1) and strong dendritic cell activation capabilities in the skin model in vitro. In vivo, the FB-Ag promoted the spread of antigen in the skin through active movement, increased the contact between Intradermal dendritic cells and antigen, and effectively activated the internal dendritic cells in the skin. In a mouse of pulmonary metastatic melanoma and in mice bearing subcutaneous melanoma tumor, the FB-Ag effectively increased antigen-specific therapeutic efficacy and produced long-lasting immune memory. More importantly, the FB-Ag also enhanced the level of COVID-19 specific antibodies in the serum and the number of memory B cells in the spleen of mice. The movement of antigen-loaded flagellate bacteria to overcome intradermal constraints may enhance the activation of intradermal dendritic cells, providing new ideas for developing intradermal vaccines.

Seasonality and meteorological factors of HIV-negative cryptococcal meningitis in Guangdong Province, China.

OBJECTIVE: Information about the seasonal characteristics of human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) is quite limited. The aim of this study was to explore the seasonality and meteorological factors of HIV-negative patients with CM. METHODS: We performed a retrospective study of 469 HIV-negative CM patients admitted to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. Their initial onset symptoms of CM occurred from January 2011 to December 2020. The temperature, precipitation, sunlight, humidity and wind speed for the corresponding period and the associated topographic, ecological type and soil type parameters data were collected. The Poisson regression model was used to determine the meteorological factors associated with CM onset. The geographical detector method was used to detect other environmental factors associated with CM onset. RESULTS: CM onset did not showed a seasonal fluctuation, but was strongly associated with mean temperature (ß = .010, p = .028) and mean relative humidity (ß = -.011, p = .006). In the rainy season, only mean wind speed remained significantly associated with CM onset (ß = -.108, p = .041). In the dry season, mean temperature (ß = .014, p = .016), mean relative humidity (ß = -.016, p = .006) and hours of sunlight (ß = -.002, p = .016) were significantly associated with CM onset. Topographic, ecological type and soil type factors did not add explanatory power. CONCLUSIONS: Our findings add the knowledge about the environmental factors of HIV-negative CM. Meteorological factors, especially temperature and humidity, may be the main environmental factors affecting the onset of HIV-negative CM.

Multi-generation study of heavy ion beam-induced mutations and agronomic trait variations to accelerate rice breeding.

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 - 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 - 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 - 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

The fertilization process in Lithocarpus dealbatus (Fagaceae) and its implication on the sexual reproduction evolution of Fagales.

MAIN CONCLUSION: The pistillate flowers of Lithocarpus dealbatus show two pollen tube (PT) arresting sites (the style-joining and micropyle) within the pistil during the postpollination-prezygotic stage. The PT, arrested at the pre-ovule stage, enhanced PT competition allowing the most compatible PTs to enter the ovary to ensure the highest fertilization success. During the shift from animal pollination to wind pollination, plants require a series of changes in reproductive traits. The mode of pollination is striking labile in Fagaceae. Lithocarpus is insect pollinated and is closely related to wind-pollinated Quercus. Little is known about the sexual reproduction of Lithocarpus. This study aimed to reveal the sexual reproduction of Lithocarpus dealbatus and to explore the evolutionary pattern of the key sexual reproduction traits to better understand their possible role in labile pollination. We found that after pollination, L. dealbatus PTs grew slowly in the style reaching style-joining in mid-January of the second year; then PT growth was arrested at style-joining for four months. Only two to three PTs resumed growth in mid-May to reach the micropyle, where PT growth ceased for one month before one PT resumed growth and passed through the micropyle to the embryo sac. Fagaceae showed a generalized mating system. Vast pollen production, small-sized pollen grains, long stigmatic receptive time, and reduced perianth were compatible with beetle pollination syndrome, representing the plesiomorphic status in Fagaceae. A large stigmatic surface and dry pollen grains linked to wind pollination might be independently derived several times in fagaceous lineages. Beetle pollination syndrome can cope with the uncertainty of pollinators to ensure conspecific pollen capture, which represents pre-adaptation status and has a selective advantage when conditions change, favouring wind pollination. The arrest of the PT at style-joining is a unique mechanism in later derived fagaceous lineages to enhance PT competition and promote outcrossing.

Physiological and Transcriptomic Analyses Reveal the Effects of Carbon-Ion Beam on Taraxacum kok-saghyz Rodin Adventitious Buds.

Taraxacum kok-saghyz Rodin (TKS) has great potential as an alternative natural-rubber (NR)-producing crop. The germplasm innovation of TKS still faces great challenges due to its self-incompatibility. Carbon-ion beam (CIB) irradiation is a powerful and non-species-specific physical method for mutation creation. Thus far, the CIB has not been utilized in TKS. To better inform future mutation breeding for TKS by the CIB and provide a basis for dose-selection, adventitious buds, which not only can avoid high levels of heterozygosity, but also further improve breeding efficiency, were irradiated here, and the dynamic changes of the growth and physiologic parameters, as well as gene expression pattern were profiled, comprehensively. The results showed that the CIB (5-40 Gy) caused significant biological effects on TKS, exhibiting inhibitory effects on the fresh weight and the number of regenerated buds and roots. Then,15 Gy was chosen for further study after comprehensive consideration. CIB-15 Gy resulted in significant oxidative damages (hydroxyl radical (OH•) generation activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and malondialdehyde (MDA) content) and activated the antioxidant system (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX)) of TKS. Based on RNA-seq analysis, the number of differentially expressed genes (DEGs) peaked at 2 h after CIB irradiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DNA-replication-/repair- (mainly up-regulated), cell-death- (mainly up-regulated), plant-hormone- (auxin and cytokinin, which are related to plant morphogenesis, were mainly down-regulated), and photosynthesis- (mainly down-regulated) related pathways were involved in the response to the CIB. Furthermore, CIB irradiation can also up-regulate the genes involved in NR metabolism, which provides an alternative strategy to elevate the NR production in TKS in the future. These findings are helpful to understand the radiation response mechanism and further guide the future mutation breeding for TKS by the CIB.

Value of optical coherence tomography measurement of macular thickness and optic disc parameters for glaucoma screening in patients with high myopia.

BACKGROUND: The basic method of glaucoma diagnosis is visual field examination, however, in patients with high myopia, the diagnosis of glaucoma is difficult. AIM: To explore the value of optical coherence tomography (OCT) for measuring optic disc parameters and macular thickness as a screening tool for glaucoma in patients with high myopia. METHODS: Visual values (contrast sensitivity, color vision, and best-corrected visual acuity) in three groups, patients with high myopia in Group A, patients with high myopia and glaucoma in Group B, and patients with high myopia suspicious for glaucoma in Group C, were compared. Optic disc parameters, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer (GCC) thickness were measured using OCT technology and used to compare the peri-optic disc vascular density of the patients and generate receiver operator characteristic (ROC) test performance curves of the RNFL and GCC for high myopia and glaucoma. RESULTS: Of a total of 98 patients admitted to our hospital from May 2018 to March 2022, totaling 196 eyes in the study, 30 patients with 60 eyes were included in Group A, 33 patients with 66 eyes were included in Group B, and 35 patients with 70 eyes were included in Group C. Data were processed for Groups A and B to analyze the efficacy of RNFL and GCC measures in distinguishing high myopia from high myopia with glaucoma. The area under the ROC curve was greater than 0.7, indicating an acceptable diagnostic value. CONCLUSION: The value of OCT measurement of RNFL and GCC thickness in diagnosing glaucoma in patients with high myopia and suspected glaucoma is worthy of development for clinical use.

Comparison and Characterization of Phenotypic and Genomic Mutations Induced by a Carbon-Ion Beam and Gamma-ray Irradiation in Soybean (Glycine max (L.) Merr.).

Soybean (Glycine max (L.) Merr.) is a nutritious crop that can provide both oil and protein. A variety of mutagenesis methods have been proposed to obtain better soybean germplasm resources. Among the different types of physical mutagens, carbon-ion beams are considered to be highly efficient with high linear energy transfer (LET), and gamma rays have also been widely used for mutation breeding. However, systematic knowledge of the mutagenic effects of these two mutagens during development and on phenotypic and genomic mutations has not yet been elucidated in soybean. To this end, dry seeds of Williams 82 soybean were irradiated with a carbon-ion beam and gamma rays. The biological effects of the M1 generation included changes in survival rate, yield and fertility. Compared with gamma rays, the relative biological effectiveness (RBE) of the carbon-ion beams was between 2.5 and 3.0. Furthermore, the optimal dose for soybean was determined to be 101 Gy to 115 Gy when using the carbon-ion beam, and it was 263 Gy to 343 Gy when using gamma rays. A total of 325 screened mutant families were detected from out of 2000 M2 families using the carbon-ion beam, and 336 screened mutant families were found using gamma rays. Regarding the screened phenotypic M2 mutations, the proportion of low-frequency phenotypic mutations was 23.4% when using a carbon ion beam, and the proportion was 9.8% when using gamma rays. Low-frequency phenotypic mutations were easily obtained with the carbon-ion beam. After screening the mutations from the M2 generation, their stability was verified, and the genome mutation spectrum of M3 was systemically profiled. A variety of mutations, including single-base substitutions (SBSs), insertion-deletion mutations (INDELs), multinucleotide variants (MNVs) and structural variants (SVs) were detected with both carbon-ion beam irradiation and gamma-ray irradiation. Overall, 1988 homozygous mutations and 9695 homozygous + heterozygous genotype mutations were detected when using the carbon-ion beam. Additionally, 5279 homozygous mutations and 14,243 homozygous + heterozygous genotype mutations were detected when using gamma rays. The carbon-ion beam, which resulted in low levels of background mutations, has the potential to alleviate the problems caused by linkage drag in soybean mutation breeding. Regarding the genomic mutations, when using the carbon-ion beam, the proportion of homozygous-genotype SVs was 0.45%, and that of homozygous + heterozygous-genotype SVs was 6.27%; meanwhile, the proportions were 0.04% and 4.04% when using gamma rays. A higher proportion of SVs were detected when using the carbon ion beam. The gene effects of missense mutations were greater under carbon-ion beam irradiation, and the gene effects of nonsense mutations were greater under gamma-ray irradiation, which meant that the changes in the amino acid sequences were different between the carbon-ion beam and gamma rays. Taken together, our results demonstrate that both carbon-ion beam and gamma rays are effective techniques for rapid mutation breeding in soybean. If one would like to obtain mutations with a low-frequency phenotype, low levels of background genomic mutations and mutations with a higher proportion of SVs, carbon-ion beams are the best choice.

Genetically engineered PD-1 displaying nanovesicles for synergistic checkpoint blockades and chemo-metabolic therapy against non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains the most frequently diagnosed lung cancer and the leading cause of cancer-related mortality worldwide. PD-1/PD-L1 axis inhibitors have changed the treatment paradigm for various cancer types, including NSCLC. However, success of these inhibitors in lung cancer clinic is severely limited by their inability to inhibit the PD-1/PD-L1 signaling axis due to heavy glycosylation and heterogeneity expression of PD-L1 in NSCLC tumor tissue. Taking advantage of the facts that tumor cell derived nanovesicles could efficiently accumulate in the homotypic tumor sites due to their innate targeting abilities and that specific and high affinity existed between PD-1 and PD-L1, we developed NSCLC targeting biomimetic nanovesicles (NV) cargos from genetically engineered NSCLC cell lines that overexpressed PD-1 (P-NV). We showed that P-NVs efficiently bound NSCLC cells in vitro and targeted tumor nodules in vivo. We further loaded P-NVs with 2-deoxy-D-glucose (2-DG) and doxorubicin (DOX), and found that these drugs co-loaded P-NVs efficiently shrank lung cancers in mouse models for both allograft and autochthonous tumor. Mechanistically, drug-loaded P-NVs efficiently caused cytotoxicity to tumor cells and simultaneously activated anti-tumor immunity function of tumor-infiltrating T cells. Our data therefore strongly argue that 2-DG and DOX co-loaded, PD-1-displaying nanovesicles is a highly promising therapy for treatment of NSCLC in clinic. STATEMENT OF SIGNIFICANCE: Lung cancer cells overexpressing PD-1 are developed for preparing nanoparticles (P-NV). PD-1s displayed on NVs enhance their homologous targeting abilities to tumor cells expressing PD-L1s. Chemotherapeutics such as DOX and 2-DG, are packaged in such nanovesicles (PDG-NV). These nanovesicles efficiently delivered chemotherapeutics to tumor nodules specifically. The synergy between DOX and 2-DG is observed in inhibiting lung cancer cells in vitro and in vivo. Importantly, 2-DG causes deglycosylation and downregulation of PD-L1 on tumor cells while PD-1 displayed on nanovesicles' membrane blocks PD-L1 on tumor cells. 2-DG loaded nanoparticles thus activate anti-tumor activities of T cells in the tumor microenvironment. Our work thus highlights the promising antitumor activity of PDG-NVs, which warrants further clinical evaluation.

Recent advances in bacterial therapeutics based on sense and response.

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.

Specialized herbivory in fossil leaves reveals convergent origins of nyctinasty.

Plants can move in various complex ways in response to external stimuli.1,2 These mechanisms include responses to environmental triggers, such as tropic responses to light or gravity and nastic responses to humidity or contact.3 Nyctinasty, the movements involving circadian rhythmic folding at night and opening at daytime of plant leaves or leaflets, has attracted the attention of scientists and the public for centuries.4,5 In his canonical work entitled The Power of Movement in Plants, Charles Darwin carried out pioneering observations to document the diverse range of movements in plants.6 His systematic examination of plants showing "sleep [folding] movements of leaves" led him to conclude that the legume family (Fabaceae) includes many more nyctinastic species than all other families combined.3 Darwin also found that a specialized motor organ, the pulvinus, is responsible for most sleep movements of plant leaves, although differential cell division and the hydrolysis of glycosides and phyllanthurinolactone also facilitate nyctinasty in some plants.7,8 However, the origin, evolutionary history, and functional benefits of foliar sleep movements remain ambiguous owing to the lack of fossil evidence for this process. Here, we document the first fossil evidence of foliar nyctinasty based on a symmetrical style of insect feeding damage (Folifenestra symmetrica isp. nov.) in gigantopterid seed-plant leaves from the upper Permian (∼259-252 Ma) of China. The pattern of insect damage indicates that the host leaves were attacked when mature but folded. Our finding reveals that foliar nyctinasty extends back to the late Paleozoic and evolved independently among various plant lineages.

A new clam shrimp (Branchiopoda: Diplostraca: Spinicaudata) from the Upper Jurassic in the Jiyuan Basin, China and its biostratigraphic significance.

A new spinicaudatan species Triglypta jiyuanensis Liao & Huang sp. nov. is described from the Upper Jurassic Maao Formation in the Jiyuan Basin, northwestern Henan Province, China. The carapace of the new species is ornamented with punctae, linear arrangements of punctae, and radial lirae. The new species differs from those of the early Triglypta forms from the Middle Jurassic but closely resembles T. jianchangensis Wang, 2014 from the Upper Jurassic Tiaojishan Formation of western Liaoning Province. Our study provides new biostratigraphic evidence supporting that the Maao and Tiaojishan formations can be correlated. Moreover, we suggest that the Yangshuzhuang Formation in the Jiyuan Basin could correlate to the Haifanggou and the Longmen formations in the Yanliao area.

The first species of Thaumatomeropidae (Insecta: Mecoptera) from the Middle Triassic of China.

Thaumatomeropidae is an enigmatic mecopteran family previously known exclusively from the Triassic Madygen entomofauna of Kyrgyzstan. Thaumatomeropids display mosaic venation, closely resembling those of Meropeidae and Eomeropidae, yet distinguished by some more primitive characters. Here we describe and illustrate a new thaumatomeropid species, Thaumatomerope sinensis Lian & Huang, sp. nov., from the late Middle Triassic Tongchuan entomofauna of the Chang 7 Member of the Yanchang Formation near the Hejiafang Village, Tongchuan City, NW China. This new species is characterized by reduced Rs branches, and some unique forking patterns, including the single posterior last branch of Rs and multi-branched anterior first branch of M. It represents the first thaumatomeropid species reported outside Kyrgyzstan, indicating a broader geographical distribution of the family. Moreover, this discovery enhances the resemblance of mecopteran components between the Tongchuan and the Madygen entomofaunas.

Simultaneous CSM-TACE with CalliSpheres® and partial splenic embolization using 8spheres® for hepatocellular carcinoma with hypersplenism: Early prospective multicenter clinical outcome.

Background: Primary hepatocellular carcinoma is often complicated with hepatitis and liver cirrhosis. Some patients develop different degrees of splenomegaly, hypersplenism and hypohepatia due to the aggravation of liver cirrhosis, which to some extent interfere with the treatment of tumors and even affect the prognosis of patients. In this study, we prospectively evaluate the efficacy and safety of simultaneous CalliSpheres® microspheres transcatheter arterial chemoembolization (CSM-TACE) and partial splenic embolization (PSE) using 8spheres® for hepatocellular carcinoma (HCC) with hypersplenism. Methods: Ninety consecutive HCC patients with hypersplenism who underwent CSM-TACE were selected: 32 patients in CSM-TACE+PSE group, and 58 patients in CSM-TACE group. The peripheral blood cell counts (leukocyte, platelet (PLT), liver function and red blood cell (RBC)), CSM-TACE and/or PSE related complications, and the tumor control rate at 1 month after CSM-TACE were compared. The survival time and prognostic factors were also observed. Results: Before CSM-TACE, there were no significant differences in sex, age, Child-Pugh grade, tumor size, and alpha-fetoprotein (AFP) between the two groups. After CSM-TACE, the PLT and white blood cell (WBC) counts in CSM-TACE+PSE group were significantly higher than those in the CSM-TACE group (P<0.05). There were no significant differences in RBC before and after treatment (P > 0.05). In the CSM-TACE group, there were no significant differences in WBC, PLT, and RBC before and after treatment (P > 0.05). There was no significant difference in liver function at 1 month after treatment between the two groups. The cholinesterase (CHE) level in the CSM-TACE+PSE group after CSM-TACE+PSE was obviously higher than that before CSM-TACE+PSE and higher than that in the CSM-TACE group (P<0.05). However, the level of CHE returned to the preoperative level 1 month after CSM-TACE in the CSM-TACE group. The objective response rate (ORR) and median overall survival (OS) in the CSM-TACE+PSE group were higher than those in the CSM-TACE group (P<0.05). The adverse reactions of the two groups were fever, abdominal pain, stomach discomfort, nausea, and vomiting, and no serious complications occurred. The degree of abdominal pain and fever in the experimental group was lower than that in the control group (P > 0.05). Conclusions: Simultaneous CSM-TACE and PSE using domestic embolization particles for HCC with hypersplenism have good safety and efficacy and has a low incidence of PSE-related adverse events, it is conducive to improving liver function reserve, and can further improve the median OS.