Breast cancer is one of the most common malignant tumors among women, which seriously threatens women’s health. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, characterized by poor prognosis, is an aggressive phenotype accounting for 15–20% of all kinds of breast cancers. Therefore, it has attracted great interest among researchers in discovering targeted therapy drugs countering HER2, and they have been considered as the pivotal therapeutic regimen for HER2-positive breast cancer patients. Nowadays, large progress has been achieved in HER2-targeted drugs, and this review categorizes them into four types according to the drug action mode, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs). The progress of HER2-targeted drugs reflects the discovery of drug targets, the screening of drug compounds, and the modification of antibodies, which offer diverse medical options and better therapeutic benefits for individual patients. In detail, we focus on the indication, administration, efficacy, strengths, and challenges of HER2-targeted drugs, concerning approved drugs and clinical trials. This review aims to provide significant references for the targeted therapeutic regimen and a more precise treatment strategy for HER2-positive breast cancer.

The interaction effects of dietary non-phytate phosphorus (NPP) and phytase on growth performance, mineral metabolism, and gene expressions of mineral transporters in broilers duodenum and kidney (0-3 weeks) were studied. The levels of NPP (0.45 %, 0.35 %, or 0.25 %) and phytase (0 or 2,500 FTU/kg) in the diets were applied in a 3 × 2 factorial arrangement to carry out rearing feeding strategies. Broilers received the diet containing 0.25 % NPP showed lower (P < 0.05) body weight gain (BWG), feed intake (FI), plasma calcium (Ca) and phosphorus (P) levels, bone attributes, and higher (P < 0.05) mortality rate than those of broilers fed diets containing 0.45 % NPP alone or in combination of phytase, 0.35 % NPP or 0.25 % NPP in combination of phytase. Significant interactions (P < 0.05) of phytase and NPP were found in BWG, FI, bone attributes, plasma Ca and P levels, and mortality rate of broiler. Broilers received the diet containing 0.25 % NPP had higher (P < 0.05) mRNA expressions of nuclear vitamin D receptors (nVDR), Calbindin-D28k (CaBP-D28k) and Plasma membrane Ca ATPase 1b (PMCA1b) in duodenum, mRNA expressions of CaBP-D28k and sodium-dependent phosphate cotransporters type IIa (NaPi-IIa) in kidney, and liver 25-hydroxylase mRNA expression than those of broilers fed diets containing 0.45 % NPP alone or in combination of phytase, 0.35 % NPP or 0.25 % NPP in combination of phytase. The interaction of NPP and phytase significantly affected (P < 0.05) the mRNA expressions of nVDR, CaBP-D28k and PMCA1b in duodenum, the mRNA expressions of CaBP-D28k and NaPi-IIa in kidney, and liver 25-hydroxylase mRNA expression. Dietary phytase supplementation improved growth performance, bone attributes, and absorption of Ca and P even if dietary NPP level dropped to 0.25 %.

The hypothalamus is the advanced center that regulates visceral activities under the cerebral cortex. It plays some key roles, such as regulating body temperature, assessing feed intake, and balancing blood glucose and endocrine gland activities. Heat stress is known to trigger a series of detrimental consequences, prominently featuring a reduction in feed intake, an elevation in body temperature, and other related phenomena. To understand the mechanisms of how heat stress affects the function of the hypothalamus, broilers were allocated to three groups: the normal control (NC) group, the heat-stress (HS) group, and the pair-fed (PF) group. The PF group was established with the aim of eliminating the confounding effect of reduced feed intake. The trial lasted for two weeks, from the age of 28 to 42 d. A total of 280 differential expressed genes (DEGs) were identified (p_adj < 0.05, |log₂(FC)| ≥ 1) among three groups, including 3 up-regulated and 112 down-regulated genes in the HS group compared to the NC group, and 3 up-regulated and 13 down-regulated genes between the PF and NC groups. Compared with the HS group, a total of 149 genes were identified in the PF group, of which 125 genes were up-regulated and 24 genes were down-regulated. Gene Ontology enrichment indicated that a subset of DEGs was involved in brain development, the central nervous system (CNS), nerve signal transduction, and calcium homeostasis. The solute carrier family 1 member A6 and solute carrier family 6 member 13, identified as down-regulated genes (p_adj < 0.05) in the HS group, were considered as key genes in Gamma-aminobutyric acid (GABA) transportation, the normal expression of which ensures that extracellular GABA is maintained at a certain level and provides the amino acids needed for metabolism. Simultaneously, the solute carrier family 13 member 4 and solute carrier family 16 member 8 were also identified as down-regulated, which indicated that heat stress resulted in disorder and physiologic derangement in the hypothalamus. Meanwhile, the anorexigenic part of pro-opiomelanocortin genes was up-regulated significantly in the HS group. The transcriptome sequencing results can help us understand the regulatory mechanism of feed intake decline in broilers under heat stress at the genetic level.

The objective of this study is investigating the effects of Lonicerae flos extract (LFE) on antioxidant status, intestinal development, and jejunum barrier function in heat-stressed broilers. Two hundred and forty male broilers (28-day-old) were assigned to normal control group (NOR, 22°C, basal diet), heat stress group (HS, 32°C, basal diet) and Lonicerae flos extract supplementation group (LFE, 32°C, basal diet with 400 mg/kg, 800 mg/kg, 1200 mg/kg LFE). Results indicated that Heat stress significantly impaired growth performance, increased serum aspartate aminotransferase (AST) and d-lactate levels, decreased jejunal mucosal total antioxidant capacity (T-AOC) and jejunal villus height (P < 0.05) throughout the entire experimental period. Although not statistically significant for growth performance, Lonicerae flos extract numerically reduced the feed-to-gain ratio by 8.5 % after 14 days. Lonicerae flos extract, particularly at 800 mg/kg, significantly mitigated the heat stress-induced elevation in serum AST and d-lactate levels and enhanced jejunal T-AOC and superoxide dismutase (SOD) activity and jejunal villus height (P < 0.05). Lonicerae flos extract activated Nrf-2 pathway, downregulated the mRNA expressions of endoplasmic reticulum stress (ERS) and apoptosis-related genes, and enhanced the mRNA expressions of tight junction proteins in jejunum mucosa of heat stressed-broilers. The 800 mg/kg dose was identified as the most effective. In conclusion, dietary LFE effectively improved intestinal integrity and antioxidant capacity in heat-stressed broiler through activating Nrf-2 pathway, alleviating ERS-dependent apoptosis and improving jejunum barrier function.

Background: Wheat is progressively utilized in animal husbandry. However, the chemical properties of wheat are influenced by breed and climate, consequently impacting its economic value and application in feed formulation. This study was conducted to evaluate the digestible energy (DE) and metabolizable energy (ME), as well as apparent total tract digestibility (ATTD) of nutrients in 17 samples of wheat for growing pigs.Methods: Fifty-one growing barrows were randomly allotted to 17 experimental diets (3 pigs in each diet). The experiment included two successive periods, and per period lasted for 12 days, including 7 days for diet adaptation, 5 days for urine and feces collection.Results: There was significant (p < 0.01) difference in DE content of 17 wheat cultivars. The DE and ME contents ranged from 16.06 to 16.88 MJ/kg DM and 15.65 to 16.36 MJ/kg DM, respectively. The coefficients variation (CV) of the chemical compositions were bulk density (3.14%), crude protein (CP) (9.00%), neutral detergent fiber (NDF) (34.60%), acid detergent fiber (ADF) (9.65%) and ether extract (EE) (10.16%) in the 17 wheat samples. Except for the ATTD of phosphorus (P), there were significant differences in the ATTD of gross energy (GE) (p = 0.01), organic matter (OM) (p = 0.02), CP (p < 0.01), NDF (p < 0.01), ADF (p < 0.01), EE (p = 0.04) and calcium (Ca) (p = 0.03) in 17 wheat cultivars.Conclusion: DE was significantly positively correlated with ME and CP content, GE was significantly negatively correlated with starch, and CP content was positively correlated with GE, DE and ME contents. Based on statistical analysis of chemical components of wheat samples, the GE, CP, starch, and bulk density are key variables for predicting effective energy, and the most suitable regression equations of DE and ME in different wheat cultivars were DE = 26.6394 − 0.6783 GE (MJ/kg) + 0.1618 CP (%) and ME = −0.3869 + 0.7788 DE (MJ/kg) + 0.0336 starch (%) + 0.0020 bulk density (g/L).