The aim of this study was to examine the effects of different modifiers on the changes in aggregates and organic carbon in acidic purple soil， providing a scientific basis for the remediation of acidic purple soil. Using purple soil as the research object， a total of six treatments were set up， including no fertilization （CK）， single fertilization （F）， fertilization with lime （SF）， fertilization with organic fertilizer （OM）， fertilization with biochar （BF）， and fertilization with distiller\'s grains ash （JZ）. We compared the composition of aggregates in acidic purple soil under the application of different modifiers， as well as the distribution pattern of organic carbon in aggregates of different particle sizes. Combined with the stability indicators of aggregates， we sought to clarify the impact of different modifiers on the structure of aggregates in acidic purple soil. The results showed that fertilization significantly increased the soil pH， with the JZ treatment being the most effective. Fertilization significantly increased soil organic matter content， with the OM treatment showing the largest increase. The BF and OM treatments significantly reduced soil bulk density， whereas the SF and BF treatments significantly increased soil moisture content （P < 0.05）. All treatments used < 0.25 mm aggregates as the dominant particle size. Fertilization could significantly increase the content of large aggregates （aggregate structure units with diameter > 0.25 mm）. At the same time， fertilization treatments significantly increased the soil geometric mean diameter （GMD）， average weight diameter （MWD）， and R0.25 value （ > 0.25 mm aggregate content） and reduced the fractal cone number （D） and aggregate destruction rate （PAD） values （P < 0.05）. Fertilization also promoted the aggregation and stability of soil aggregates， with the OM treatment having the greatest effect. Compared with that in the CK treatment， fertilization could significantly increase soil organic carbon content by 31.71%-209.67%， with the OM treatment showing the most significant change. Different treatments of soil organic carbon were mainly distributed in large aggregates. Compared with that in the CK treatment， each treatment significantly increased the contribution rate of organic carbon in large aggregates by 19.34%-47.76%， with the OM treatment having the most significant effect （P < 0.05）. In general， chemical fertilizer combined with organic fertilizer could promote the formation of large aggregates in acidic purple soil， improve the stability of soil aggregates， and increase the content of soil organic carbon， which is an effective measure to improve the soil structure and improve the quality of acidic purple soil.

Patients with the genotype of β0/β0 for β-thalassemia (β-thal) usually behave as β-thal major (β-TM) phenotype which is transfusion-dependent. The pathophysiology of β-thal is the imbalance between α/β-globin chains. The degree of α/β-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of β-TM. We report a Chinese child who had homozygous β0-thal and a heterozygous KLF1 mutation. The patient had a moderate anemia since 6 months old, keeping a baseline Hb value of 8.0-9.0 g/dL. She had normal development except for a short stature (3rd percentile) until 6 years old, when splenomegaly and facial bone deformities occurred. Although genetic alteration of KLF1 expression in β0/β0 patients can result in some degree of disease alleviation, our case shows that it is insufficient to ameliorate satisfactorily the presentation. This point should be borne in mind for physicians who provide the genetic counseling and prenatal diagnosis to at-risk families.

High mercury (Hg) bioaccumulation in crops such as rice in Hg-contaminated areas presents a potential health hazard to humans and wildlife. To develop a safe alternative technique, bacillus-inoculated biofertilizer, citric acid, earthworms, and selenium-modified activated clay were compared for their ability to regulate Hg bioaccumulation in Pennisetum giganteum (P. giganteum). This biofertilizer significantly increased Bacillus sp. abundance in the soil by 157.12%, resulting in the removal of 27.52% of water-soluble Hg fractions through volatilization and adsorption mechanisms. The variation in bioavailable Hg in the soil significantly reduced the total Hg concentration in P. giganteum young leaves, old leaves, stems, and roots of P. giganteum by 74.14%, 48.08%, 93.72%, and 50.91%, respectively (p < 0.05), which is lower than the Chinese feed safety standard (100 ng g-1). The biofertilizer inhibitory potential was highly consistent with that of the selenium-modified activated clay. Biofertilizers significantly reduced the methylmercury concentration in various P. giganteum tissues (p < 0.05), whereas selenium-modified activated clay failed to achieve a comparable effect. This biofertilizer-assisted planting pattern can achieve an economic income quadruple that of the rice planting pattern in the Hg-contaminated paddy fields. Because of its significant environmental and financial applications, the biofertilizer-assisted planting pattern is expected to replace Hg-contaminated paddy fields.

To screen environmentally friendly and efficient Cd pollution remediation material, the effects of BC and BF on soil Cd bio-availability and cotton Cd absorption were analyzed under Cd exposure. Besides, the differences in metabolic mechanisms by which biochar (BC) and biofertilizer (BF) affect Cd-contaminated soil and cotton were also analyzed. The results showed that the application of BC and BF increased cotton dry matter accumulation, boll number, and single boll weight, and reduced the Cd content in cotton roots, stems, leaves, and bolls. At harvest, the Cd content in cotton roots in the BC and BF groups reduced by 15.23% and 16.33%, respectively, compared with that in the control. This was attributed to the conversion of carbonate-bound Cd (carbon-Cd) and exchangeable Cd (EX-Cd) by BC and BF into residual Cd (Res-Cd). It should be noted that the soil available Cd (Ava-Cd) content in the BF group was lower than that in the BC group. The metabolomic analysis results showed that for BC vs BF, the relative abundance of differential metabolites Caffeic acid, Xanthurenic acid, and Shikimic acid in soil and cotton roots were up-regulated. Mantel test found that cotton root exudate l-Histinine was correlated with the enrichment of Cd in various organs of cotton. Therefore, the application of BC and BF can alleviate Cd stress by reducing soil Ava-Cd content and cotton\'s Cd uptake, and BF is superior to BC in reducing Cd content in soil and cotton organs. This study will provide a reference for the development of efficient techniques for the remediation of Cd-polluted alkaline soil, and provide a basis for subsequent metagenomics analysis.

The contents and kinds of oxygen-containing functional groups are very significant when preparing cationic hydrochar coagulants via graft copolymerization. Herein, the hydrothermal conditions to produce sludge-based hydrochar (SBC) precursors were optimized by introducing different kinds and amounts of modifying agents (i.e., HCOOH, citric acid (CA), H2SO4, and H2O2), then the surface properties and flocculation performance of derived cationic coagulants (SBC-g-DMC) were studied. Results showed that the utilization of four modifiers raised the acidic groups on the SBC surface; thereinto, the presence of CA could evidently increase the content of phenolic hydroxyl groups. After DMC monomer grafting, the formed coagulants possess positive zeta potentials over a wide pH range (i.e., 3.0 ~ 11.0), showing a typical cationic property. The grafting ratio and efficiency, as well as the cationic degree of coagulants prepared with different SBC precursors follow a descending order of SBCCA-g-DMC > [Formula: see text]-g-DMC > SBCHCOOH-g-DMC > [Formula: see text]-g-DMC; thus, SBCCA-g-DMC coagulant with the best grafting result shows a superior flocculation performance. When a dosage of 4 mg/L was adopted, the average turbidity removal rate of SBCCA-g-DMC could reach up to 94.44%. Meanwhile, due to the possible and robust oxidation with the initiator, H2O2 seems not a perfect modifier for SBC preparation. This study could provide an essential reference for the optimal synthesis of SBC and its based coagulants for organic matter recovery and pollutant removal.

To further promote the development of research on direct-to-plant SBS-modified asphalt, this article analyzes the development of direct-to-plant SBS modifiers. Starting from the material composition and mechanism of action, common direct-to-plant SBS modifiers were analyzed and classified into four categories based on their mechanism of action, including the instant dissolution principle, intramolecular lubrication principle, non-granulation principle, and vulcanization principle. From the evaluation of the modification effect, the method of studying the performance of direct-to-plant SBS-modified asphalt is summarized, including fluorescence microscopy, AFM technology, and molecular dynamics simulation technology. From the perspective of practical application, the construction process of direct-to-plant SBS-modified asphalt was discussed, including the design stage, raw material preparation stage, mix design stage, and on-site construction stage. The results show that common direct-to-plant SBS modifiers are primarily SBS with a small particle size (less than 200 mesh) or specific model, supplemented by additives (EVA, naphthenic oil, sulfur, petroleum resin, etc.), which improve melting efficiency and lubricity or make it undergo vulcanization reaction, change the proportion of asphalt components, and improve stability. In the evaluation of the modification effect of direct-to-plant SBS-modified asphalt, the disparity of the direct-to-plant SBS modifier is determined by observing the particle residue after dry mixing. Macroscopic indexes of modified asphalt and modified asphalt mixture are used to determine the cross-linking effect of direct-to-plant SBS modifier and asphalt, and the modification mechanism and modification effect of wet SBS modifier are evaluated at the microscopic level. The development of direct-to-plant SBS-modified asphalt should combine the characteristics of direct-to-plant SBS modifiers and the attributes of field application, targeted research, and the development of high-performance direct-to-plant SBS modifiers and complete production technologies applicable to different regions, strengthen the improvement of modification effect evaluation, and form a complete theoretical system.

The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS.
The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646.
A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS.
Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.

The adhesion between asphalt binder and aggregate is very important to the performance and durability of asphalt pavement. In order to explore the characterisation of modified asphalt binder in microstructure during aging and rejuvenation, the virgin asphalt binder and three kinds of modified asphalt binder (styrene-butadiene-styrene block copolymer (SBS), rubber powder and high viscosity and high elasticity [HVHE] modifier) in different aging and rejuvenation condition were prepared. The micromorphology and surface adhesion were measured by atomic force microscopy. The average roughness value was used as the index to evaluate the micromorphology of asphalt binder. The surface adhesion was used as the index to evaluate the adhesion properties of asphalt binder. Results show that the \"bee\" structure of SBS-modified asphalt binder increased slightly after long-term aging, and the recovery effect of aromatics oil was the closest to that of the unaged one. The rubber powder-modified asphalt binder and HVHE-modified asphalt binder showed the spot structure. And no matter for short-term aging or long-term aging, aromatics oil had the best recovery effect on micro morphology. The adhesion of the three modified asphalts would decrease gradually after aging. The effects of three kinds of rejuvenator on the adhesion of SBS-modified asphalt binder and rubber powder-modified asphalt binder were different. Rejuvenator, aromatic oil and warm mix asphalt mixture (WMA) additive could rejuvenate the loss of adhesion of HVHE-modified asphalt binder to a certain extent.

Age at onset of amyotrophic lateral sclerosis (ALS) is highly variable (eg, 27-74 years in carriers of the G4C2-expansion in C9orf72). It might be influenced by environmental and genetic factors via the modulation of DNA methylation (DNAm) at CpG-sites. Hence, we combined an epigenetic and genetic approach to test the hypothesis that some common single nucleotide polymorphisms (SNPs) at CpG-sites (CpG-SNPs) could modify ALS age of onset. Our genome-wide DNAm analysis suggested three CpG-SNPs whose DNAm levels are significantly associated with age of onset in 249 ALS patients (q < 0.05). Next, genetic analysis validated the association of rs4970944 with age of onset in the discovery (n = 469; P = 0.025) and replication (n = 4160; P = 0.007) ALS cohorts. A meta-analysis of the cohorts combined showed that the median onset in AA-carriers is two years later than in GG-carriers (n = 4629; P = 0.0012). A similar association was observed with its tagging SNPs, implicating a 16 Kb region at the 1q21.3 locus as a modifier of ALS age of onset. Notably, rs4970944 genotypes are also associated with age of onset in C9orf72-carriers (n = 333; P = 0.025), suggesting that each A-allele delays onset by 1.6 years. Analysis of Genotype-Tissue Expression data revealed that the protective A-allele is linked with the reduced expression of CTSS in cerebellum (P = 0.00018), which is a critical brain region in the distributed neural circuits subserving motor control. CTSS encodes cathepsin S protein playing a key role in antigen presentation. In conclusion, we identified a 16 Kb locus tagged by rs4970944 as a modifier of ALS age of onset. Our findings support the role of antigen presenting processes in modulating age of onset of ALS and suggest potential drug targets (eg, CTSS). Future replication studies are encouraged to validate the link between the locus tagged by rs4970944 and age of onset in independent ALS cohorts, including different ethnic groups.

UNASSIGNED: To report the phenotypic heterogeneity of GJB2 c.235delC homozygotes associated with post-lingual and/or milder hearing loss, and explore the possible mechanism of these unconditional phenotypes.
UNASSIGNED: Mutation screening of GJB2 was performed on all ascertained members from Family 1006983 and three sporadic patients by polymerase chain reaction (PCR) amplification and Sanger sequencing. Next generation sequencing (NGS) was successively performed on some of the affected members and normal controls from Family 1006983 to explore additional possible genetic codes. Reverse transcriptase-quantitative PCR was conducted to test the expression of Connexin30.
UNASSIGNED: We identified a Chinese autosomal recessive hearing loss family with the GJB2 c.235delC homozygous mutation, affected members from which had post-lingual moderate to profound hearing impairment, and three sporadic patients with post-lingual moderate hearing impairment, instead of congenital profound hearing loss. NGS showed no other particular variants. Overexpression of Connexin30 in some of these cases was verified.
UNASSIGNED: Post-lingual and/or moderate hearing impairment phenotypes of GJB2 c.235delC homozygotes are not the most common phenotype, revealing the heterogeneity of GJB2 pathogenic mutations. To determine the possible mechanism that rescues part of the hearing or postpones onset age of these cases, more cases are required to confirm both Connexin30 overexpression and the existence of modifier genes.