Surface activity of humic acid (HA) and its six sub-fractions isolated from forest soil were characterized by surface tension measurements, dynamic light scattering, and laser doppler electrophoresis. The surface tension of HA sub-fractions decreased from 72.4 mN·m-1 to 36.8 mN·m-1 with the increasing concentration from 0 to 20000 mg·L-1. The critical micelle concentration (CMC) of HA and its sub-fractions ranged from 216 to 1024 mg·L-1 with the multiple linear regression equation of CMC = 18896–6.9×C–296×alkyl-C–331×aromatic-C–17019×H/C+4054×HB/HI (p < 0.05). The Z-average particle size ranges from 108.2 nm to 186.9 nm. The maximum particle size was 5000 nm after filtered with a membrane of 0.45 μm, indicating HA and its sub-fractions progressed self-assembly during 2000 mg·L-1, pH = 6.86. The number-base particle size distribution of HA sub-fractions was identified as four peaks by Gaussian model, and the aggregate sizes were mainly in six clusters including 2 ± 1 nm, 5 ± 2 nm, 10 ± 3 nm, 21 ± 8 nm, 40 ± 10 nm, and > 50 nm indicating multiple aggregations of different particle sizes in the HA fractions solution.

In order to improve the adaptability of broilers to low-temperature environments and their ability to resist acute cold stress (ACS), 240 one-day-old broilers were selected and randomly divided into three groups. The control treatment (CC) was raised at the conventional feeding temperature from 1-43 days (d), the cold stimulation treatments (CS) were kept at 3 °C below the temperature of CC at 1-d intervals for 3 and 6 hours from 15 to 35 d, namely CS3 and CS6, respectively. Then all broilers were kept at 20 °C from 36 to 43 d. ACS was then carried out at 44 d, and the ambient temperature was dropped to 10 °C for 6 hours. The study investigated the production perfor-mance, as well as levels of intestinal barrier genes (including Claudin-1, E-cadherin, Occludin, ZO-1, ZO-2 and Mucin2), secretory IgA in duodenum and jejunum, and immunoglobulins (IgA and IgG) in serum. The results showed that IMCS could increase the daily weight gain and decrease the feed conversion ratio. During the IMCS, the expression levels of intestinal barrier genes were up-regulated and the content of secretory IgA was increased. When IMCS ceased for one week, the level of immunoglobulins in serum stabilized, and the expression levels of Occludin, ZO-2 and Mucin2 still maintained high levels. After ACS, broilers that received IMCS training maintained the high levels of intestinal barrier genes and secretory IgA.

Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species which includes B. burgdorferi, B. afzelii, and B. garinii. The majority of patients with early LD can be cured by standard treatment, yet some still suffer from post-treatment Lyme disease syndrome (PTLDS). The presence of Borrelia persisters has been proposed as a contributing factor, which cannnot be completely killed by the currently used antibiotics for Lyme disease. Finding new pharmaceuticals targeting Borrelia persisters is crucial in developing more effective treatment. Here, we first confirmed the existence of persisters in cultures of B. garinii and B. afzelii and then conducted high-throughput screening of a custom drug library against persister-rich stationary-phase cultures of B. garinii and B. afzelii. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs, and topical antibiotics along with some other natural compounds were identified to have strong potential in killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA’s target is the cell membrane where HA-triggered reactive oxygen species (ROS) generation took place in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against Gram-positive and Gram-negative bacteria. Identification of the above-mentioned drug candidates may help to develop more effective therapies for LD.

A prior investigation revealed that a lack of Zinc (Zn) could hinder the intestinal cell proliferation in broiler chickens; however, the mechanisms responsible for this effect remain unclear. We aimed to investigate the possible mechanisms of dietary Zn deficiency in inhibiting the jejunal cell proliferation of broilers. For this study, a total of 112 chickens (21 d old) were randomly divided into two treatments (n = 7, 8 chickens per replicate cage): control (CON) and Zn deficiency groups. The duration of feeding was 21 d. Chickens in the CON group were provided with a basal diet containing an extra addition of 40 mg Zn/kg in the form of Zn sulfate, whereas chickens in the Zn deficiency group were given the basal diet with no Zn supplementation. The results indicated that, in comparison to the CON, Zn deficiency increased (P < 0.05) duodenal and jejunal crypt depth (CD) of broilers on d 28 and jejunal and ileal CD on d 35, and decreased (P < 0.05) duodenal, jejunal and ileal villus height/crypt depth (VH/CD) on d 28 and jejunal VH, jejunal and ileal villus surface area and VH/CD on d 35. Furthermore, Zn deficiency decreased (P < 0.0001) the amount of proliferating cell nuclear antigen positive cells, and down-regulated (P < 0.01) mRNA or protein expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K, phosphorylated serine threonine kinase (AKT), phosphorylated mechanistic target of rapamycin (mTOR), G protein-coupled receptor 39 (GPR39), and extracellular regulated protein kinase, but up-regulated (P < 0.05) mRNA or protein expression levels of P38 mitogen activated protein kinase, c-jun N-terminal kinase (JNK) 1 and JNK2 and phosphorylated Protein Kinase C in the jejunum of broilers on d 42. It was concluded that dietary Zn deficiency inhibited the cell proliferation possibly via GPR39-mediated suppression of PI3K/AKT/mTOR signaling pathway in the jejunum of broilers.

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the vaccine design with broad-spectrum potential.